Novel nucleic acids and polypeptides

ABSTRACT

The present invention provides novel nucleic acids, novel polypeptide sequences encoded by these nucleic acids and uses thereof.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part application of U.S. patent application Ser. No. 09/552,929, filed Apr. 18, 2000, Attorney Docket No. 791, incorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION

[0002] 1. TECHNICAL FIELD

[0003] The present invention provides novel polynucleotides and proteins encoded by such polynucleotides, along with uses for these polynucleotides and proteins, for example in therapeutic, diagnostic and research methods.

[0004] 2. BACKGROUND

[0005] Technology aimed at the discovery of protein factors (including e.g., cytokines, such as lympholkines, interferons, CSFs, chemokines, and interleukins) has matured rapidly over the past decade. The now routine hybridization cloning and expression cloning techniques clone novel polynucleotides “directly” in the sense that they rely on information directly related to the discovered protein (i.e., partial DNA/amino acid sequence of the protein in the case of hybridization cloning; activity of the protein in the case of expression cloning). More recent “indirect” cloning techniques such as signal sequence cloning, which isolates DNA sequences based on the presence of a now well-recognized secretory leader sequence motif, as well as various PCR-based or low stringency hybridization-based cloning techniques, have advanced the state of the art by making available large numbers of DNA/amino acid sequences for proteins that are known to have biological activity, for example, by virtue of their secreted nature in the case of leader sequence cloning, by virtue of their cell or tissue source in the case of PCR-based techniques, or by virtue of structural similarity to other genes of known biological activity.

[0006] Identified polynucleotide and polypeptide sequences have numerous applications in, for example, diagnostics, forensics, gene mapping; identification of mutations responsible for genetic disorders or other traits, to assess biodiversity, and to produce many other types of data and products dependent on DNA and amino acid sequences.

SUMMARY OF THE INVENTION

[0007] The compositions of the present invention include novel isolated polypeptides, novel isolated polynucleotides encoding such polypeptides, including recombinant DNA molecules, cloned genes or degenerate variants thereof, especially naturally occurring variants such as allelic variants, antisense polynucleotide molecules, and antibodies that specifically recognize one or more epitopes present on such polypeptides, as well as hybridomas producing such antibodies.

[0008] The compositions of the present invention additionally include vectors, including expression vectors, containing the polynucleotides of the invention, cells genetically engineered to contain such polynucleotides and cells genetically engineered to express such polynucleotides.

[0009] The present invention relates to a collection or library of at least one novel nucleic acid sequence assembled from expressed sequence tags (ESTs) isolated mainly by sequencing by hybridization (SBH), and in some cases, sequences obtained from one or more public databases. The invention relates also to the proteins encoded by such polynucleotides, along with therapeutic, diagnostic and research utilities for these polynucleotides and proteins. These nucleic acid sequences are designated as SEQ ID NO: 1-91 and are provided in the Sequence Listing. In the nucleic acids provided in the Sequence Listing, A is adenosine; C is cytosine; G is guanosine; T is thymine; and N is any of the four bases. In the amino acids provided in the Sequence Listing, * corresponds to the stop codon.

[0010] The nucleic acid sequences of the present invention also include, nucleic acid sequences that hybridize to the complement of SEQ ID NO: 1-91 under stringent hybridization conditions; nucleic acid sequences which are allelic variants or species homologues of any of the nucleic acid sequences recited above, or nucleic acid sequences that encode a peptide comprising a specific domain or truncation of the peptides encoded by SEQ ID NO: 1-91. A polynucleotide comprising a nucleotide sequence having at least 90% identity to an identifying sequence of SEQ ID NO: 1-91 or a degenerate variant or fragment thereof. The identifying sequence can be 100 base pairs in length.

[0011] The nucleic acid sequences of the present invention also include the sequence information from the nucleic acid sequences of SEQ ID NO: 1-91. The sequence information can be a segment of any one of SEQ ID NO: 1-91 that uniquely identifies or represents the sequence information of SEQ ID NO: 1-91.

[0012] A collection as used in this application can be a collection of only one polynucleotide. The collection of sequence information or identifying information of each sequence can be provided on a nucleic acid array. In one embodiment, segments of sequence information is provided on a nucleic acid array to detect the polynucleotide that contains the segment. The array can be designed to detect full-match or mismatch to the polynucleotide that contains the segment. The collection can also be provided in a computer-readable format.

[0013] This invention also includes the reverse or direct complement of any of the nucleic acid sequences recited above; cloning or expression vectors containing the nucleic acid sequences; and host cells or organisms transformed with these expression vectors. Nucleic acid sequences (or their reverse or direct complements) according to the invention have numerous applications in a variety of techniques known to those skilled in the art of molecular biology, such as use as hybridization probes, use as primers for PCR, use in an array, use in computer-readable media, use in sequencing full-length genes, use for chromosome and gene mapping, use in the recombinant production of protein, and use in the generation of anti-sense DNA or RNA, their chemical analogs and the like.

[0014] In a preferred embodiment, the nucleic acid sequences of SEQ ID NO: 1-91 or novel segments or parts of the nucleic acids of the invention are used as primers in expression assays that are well known in the art. In a particularly preferred embodiment, the nucleic acid sequences of SEQ ID NO: 1-91 or novel segments or parts of the nucleic acids provided herein are used in diagnostics for identifying expressed genes or, as well known in the art and exemplified by Vollrath et al., Science 258:52-59 (1992), as expressed sequence tags for physical mapping of the human genome.

[0015] The isolated polynucleotides of the invention include, but are not limited to, a polynucleotide comprising any one of the nucleotide sequences set forth in SEQ ID NO: 1-91; a polynucleotide comprising any of the full length protein coding sequences of SEQ ID NO: 1-91; and a polynucleotide comprising any of the nucleotide sequences of the mature protein coding sequences of SEQ ID NO: 1-91. The polynucleotides of the present invention also include, but are not limited to, a polynucleotide that hybridizes under stringent hybridization conditions to (a) the complement of any one of the nucleotide sequences set forth in SEQ ID NO: 1-91; (b) a nucleotide sequence encoding any one of the amino acid sequences set forth in the Sequence Listing; (c) a polynucleotide which is an allelic variant of any polynucleotides recited above; (d) a polynucleotide which encodes a species homolog (e.g. orthologs) of any of the proteins recited above; or (e) a polynucleotide that encodes a polypeptide comprising a specific domain or truncation of any of the polypeptides comprising an amino acid sequence set forth in the Sequence Listing.

[0016] The isolated polypeptides of the invention include, but are not limited to, a polypeptide comprising any of the amino acid sequences set forth in the Sequence Listing; or the corresponding full length or mature protein. Polypeptides of the invention also include polypeptides with biological activity that are encoded by (a) any of the polynucleotides having a nucleotide sequence set forth in SEQ ID NO: 1-91; or (b) polynucleotides that hybridize to the complement of the polynucleotides of (a) under stringent hybridization conditions. Biologically or immunologically active variants of any of the polypeptide sequences in the Sequence Listing, and “substantial equivalents” thereof (e.g., with at least about 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% or 99% amino acid sequence identity) that preferably retain biological activity are also contemplated. The polypeptides of the invention may be wholly or partially chemically synthesized but are preferably produced by recombinant means using the genetically engineered cells (e.g. host cells) of the invention.

[0017] The invention also provides compositions comprising a polypeptide of the invention. Polypeptide compositions of the invention may further comprise an acceptable carrier, such as a hydrophilic, e.g., pharmaceutically acceptable, carrier.

[0018] The invention also provides host cells transformed or transfected with a polynucleotide of the invention.

[0019] The invention also relates to methods for producing a polypeptide of the invention comprising growing a culture of the host cells of the invention in a suitable culture medium under conditions permitting expression of the desired polypeptide, and purifying the polypeptide from the culture or from the host cells. Preferred embodiments include those in which the protein produced by such process is a mature form of the protein.

[0020] Polynucleotides according to the invention have numerous applications in a variety of techniques known to those skilled in the art of molecular biology. These techniques include use as hybridization probes, use as oligomers, or primers, for PCR, use for chromosome and gene mapping, use in the recombinant production of protein, and use in generation of anti-sense DNA or RNA, their chemical analogs and the like. For example, when the expression of an mRNA is largely restricted to a particular cell or tissue type, polynucleotides of the invention can be used as hybridization probes to detect the presence of the particular cell or tissue mRNA in a sample using, e.g., in situ hybridization.

[0021] In other exemplary embodiments, the polynucleotides are used in diagnostics as expressed sequence tags for identifying expressed genes or, as well known in the art and exemplified by Vollrath et al., Science 258:52-59 (1992), as expressed sequence tags for physical mapping of the human genome.

[0022] The polypeptides according to the invention can be used in a variety of conventional procedures and methods that are currently applied to other proteins. For example, a polypeptide of the invention can be used to generate an antibody that specifically binds the polypeptide. Such antibodies, particularly monoclonal antibodies, are useful for detecting or quantitating the polypeptide in tissue. The polypeptides of the invention can also be used as molecular weight markers, and as a food supplement.

[0023] Methods are also provided for preventing, treating, or ameliorating a medical condition which comprises the step of administering to a mammalian subject a therapeutically effective amount of a composition comprising a polypeptide of the present invention and a pharmaceutically acceptable carrier.

[0024] In particular, the polypeptides and polynucleotides of the invention can be utilized, for example, in methods for the prevention and/or treatment of disorders involving aberrant protein expression or biological activity.

[0025] The present invention further relates to methods for detecting the presence of the polynucleotides or polypeptides of the invention in a sample. Such methods can, for example, be utilized as part of prognostic and diagnostic evaluation of disorders as recited herein and for the identification of subjects exhibiting a predisposition to such conditions. The invention provides a method for detecting the polynucleotides of the invention in a sample, comprising contacting the sample with a compound that binds to and forms a complex with the polynucleotide of interest for a period sufficient to form the complex and under conditions sufficient to form a complex and detecting the complex such that if a complex is detected, the polynucleotide of interest is detected. The invention also provides a method for detecting the polypeptides of the invention in a sample comprising contacting the sample with a compound that binds to and forms a complex with the polypeptide under conditions and for a period sufficient to form the complex and detecting the formation of the complex such that if a complex is formed, the polypeptide is detected.

[0026] The invention also provides kits comprising polynucleotide probes and/or monoclonal antibodies, and optionally quantitative standards, for carrying out methods of the invention. Furthermore, the invention provides methods for evaluating the efficacy of drugs, and monitoring the progress of patients, involved in clinical trials for the treatment of disorders as recited above.

[0027] The invention also provides methods for the identification of compounds that modulate (i.e., increase or decrease) the expression or activity of the polynucleotides and/or polypeptides of the invention. Such methods can be utilized, for example, for the identification of compounds that can ameliorate symptoms of disorders as recited herein. Such methods can include, but are not limited to, assays for identifying compounds and other substances that interact with (e.g., bind to) the polypeptides of the invention. The invention provides a method for identifying a compound that binds to the polypeptides of the invention comprising contacting the compound with a polypeptide of the invention in a cell for a time sufficient to form a polypeptide/compound complex, wherein the complex drives expression of a reporter gene sequence in the cell; and detecting the complex by detecting the reporter gene sequence expression such that if expression of the reporter gene is detected the compound the binds to a polypeptide of the invention is identified.

[0028] The methods of the invention also provides methods for treatment which involve the administration of the polynucleotides or polypeptides of the invention to individuals exhibiting symptoms or tendencies. In addition, the invention encompasses methods for treating diseases or disorders as recited herein comprising administering compounds and other substances that modulate the overall activity of the target gene products. Compounds and other substances can effect such modulation either on the level of target gene/protein expression or target protein activity.

[0029] The polypeptides of the present invention and the polynucleotides encoding them are also useful for the same functions known to one of skill in the art as the polypeptides and polynucleotides to which they have homology (set forth in Table 1); for which they have a signature region (as set forth in Table 3); or for which they have homology to a gene family (as set forth in Table 4). If no homology is set forth for a sequence, then the polypeptides and polynucleotides of the present invention are useful for a variety of applications, as described herein, including use in arrays for detection.

DETAILED DESCRIPTION OF THE INVENTION DEFINITIONS

[0030] It must be noted that as used herein and in the appended claims, the singular forms “a”, “an” and “the” include plural references unless the context clearly dictates otherwise.

[0031] The term “active” refers to those forms of the polypeptide which retain the biologic and/or immunologic activities of any naturally occurring polypeptide. According to the invention, the terms “biologically active” or “biological activity” refer to a protein or peptide having structural, regulatory or biochemical functions of a naturally occurring molecule. Likewise “immunologically active” or “immunological activity” refers to the capability of the natural, recombinant or synthetic polypeptide to induce a specific immune response in appropriate animals or cells and to bind with specific antibodies.

[0032] The term “activated cells” as used in this application are those cells which are engaged in extracellular or intracellular membrane trafficking, including the export of secretory or enzymatic molecules as part of a normal or disease process.

[0033] The terms “complementary” or “complementarity” refer to the natural binding of polynucleotides by base pairing. For example, the sequence 5′-AGT-3′ binds to the complementary sequence 3′-TCA-5′. Complementarity between two single-stranded molecules may be “partial” such that only some of the nucleic acids bind or it may be “complete” such that total complementarity exists between the single stranded molecules. The degree of complementarity between the nucleic acid strands has significant effects on the efficiency and strength of the hybridization between the nucleic acid strands.

[0034] The term “embryonic stem cells (ES)” refers to a cell that can give rise to many differentiated cell types in an embryo or an adult, including the germ cells. The term “germ line stem cells (GSCs)” refers to stem cells derived from primordial stem cells that provide a steady and continuous source of germ cells for the production of gametes. The term “primordial germ cells (PGCs)” refers to a small population of cells set aside from other cell lineages particularly from the yolk sac, mesenteries, or gonadal ridges during embryogenesis that have the potential to differentiate into germ cells and other cells. PGCs are the source from which GSCs and ES cells are derived The PGCs, the GSCs and the ES cells are capable of self-renewal. Thus these cells not only populate the germ line and give rise to a plurality of terminally differentiated cells that comprise the adult specialized organs, but are able to regenerate themselves.

[0035] The term “expression modulating fragment,” EMF, means a series of nucleotides which modulates the expression of an operably linked ORF or another EMF.

[0036] As used herein, a sequence is said to “modulate the expression of an operably linled sequence” when the expression of the sequence is altered by the presence of the EMF. EMFs include, but are not limited to, promoters, and promoter modulating sequences (inducible elements). One class of EMFs are nucleic acid fragments which induce the expression of an operably linked ORF in response to a specific regulatory factor or physiological event.

[0037] The termns “nucleotide sequence” or “nucleic acid” or “polynucleotide” or “oligonculeotide” are used interchangeably and refer to a heteropolymer of nucleotides or the sequence of these nucleotides. These phrases also refer to DNA or RNA of genomic or synthetic origin which may be single-stranded or double-stranded and may represent the sense or the antisense strand, to peptide nucleic acid (PNA) or to any DNA-like or RNA-like material. It is contemplated that where the polynucleotide is RNA, the T (thymine) in the sequences provided herein is substituted with U (uracil). Generally, nucleic acid segments provided by this invention may be assembled from fragments of the genome and short oligonucleotide linkers, or from a series of oligonucleotides, or from individual nucleotides, to provide a synthetic nucleic acid which is capable of being expressed in a recombinant transcriptional unit comprising regulatory elements derived from a microbial or viral operon, or a eukaryotic gene.

[0038] The terms “oligonucleotide fragment” or a “polynucleotide fragment”, “portion,” or “segment” or “probe” or “primer” are used interchangeable and refer to a sequence of nucleotide residues which are at least about 5 nucleotides, more preferably at least about 7 nucleotides, more preferably at least about 9 nucleotides, more preferably at least about 11 nucleotides and most preferably at least about 17 nucleotides. The fragment is preferably less than about 500 nucleotides, preferably less than about 200 nucleotides, more preferably less than about 100 nucleotides, more preferably less than about 50 nucleotides and most preferably less than 30 nucleotides. Preferably the probe is from about 6 nucleotides to about 200 nucleotides, preferably from about 15 to about 50 nucleotides, more preferably from about 17 to 30 nucleotides and most preferably from about 20 to 25 nucleotides. Preferably the fragments can be used in polymerase chain reaction (PCR), various hybridization procedures or microarray procedures to identify or amplify identical or related parts of mRNA or DNA molecules. A fragment or segment may uniquely identify each polynucleotide sequence of the present invention. Preferably the fragment comprises a sequence substantially similar to any one of SEQ ID NOs: 1-91.

[0039] Probes may, for example, be used to determine whether specific mRNA molecules are present in a cell or tissue or to isolate similar nucleic acid sequences from chromosomal DNA as described by Walsh et al. (Walsh, P.S. et al., 1992, PCR Methods Appl 1:241-250). They may be labeled by nick translation, Klenow fill-in reaction, PCR, or other methods well known in the art. Probes of the present invention, their preparation and/or labeling are elaborated in Sambrook, J. et al., 1989, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, NY; or Ausubel, F. M. et al., 1989, Current Protocols in Molecular Biology, John Wiley & Sons, New York N.Y., both of which are incorporated herein by reference in their entirety.

[0040] The nucleic acid sequences of the present invention also include the sequence information from the nucleic acid sequences of SEQ ID NOs: 1-91. The sequence information can be a segment of any one of SEQ ID NOs: 1-91 that uniquely identifies or represents the sequence information of that sequence of SEQ ID NO: 1-91. One such segment can be a twenty-mer nucleic acid sequence because the probability that a twenty-mer is fully matched in the human genome is 1 in 300. In the human genome, there are three billion base pairs in one set of chromosomes. Because 4²⁰ possible twenty-mers exist, there are 300 times more twenty-mers than there are base pairs in a set of human chromosome. Using the same analysis, the probability for a seventeen-mer to be fully matched in the human genome is approximately 1 in 5. When these segments are used in arrays for expression studies, fifteen-mer segments can be used. The probability that the fifteen-mer is fully matched in the expressed sequences is also approximately one in five because expressed sequences comprise less than approximately 5% of the entire genome sequence.

[0041] Similarly, when using sequence information for detecting a single mismatch, a segment can be a twenty-five mer. The probability that the twenty-five mer would appear in a human genome with a single mismatch is calculated by multiplying the probability for a fall match (1÷4²⁵) times the increased probability for mismatch at each nucleotide position (3×25). The probability that an eighteen mer with a single mismatch can be detected in an array for expression studies is approximately one in five. The probability that a twenty-mer with a single mismatch can be detected in a human genome is approximately one in five.

[0042] The term “open reading frame,” ORF, means a series of nucleotide triplets coding for amino acids without any termination codons and is a sequence translatable into protein.

[0043] The terms “operably linked” or “operably associated” refer to functionally related nucleic acid sequences. For example, a promoter is operably associated or operably linked with a coding sequence if the promoter controls the transcription of the coding sequence. While operably linked nucleic acid sequences can be contiguous and in the same reading frame, certain genetic elements e.g. repressor genes are not contiguously linked to the coding sequence but still control transcription/translation of the coding sequence.

[0044] The term “pluripotent” refers to the capability of a cell to differentiate into a number of differentiated cell types that are present in an adult organism. A pluripotent cell is restricted in its differentiation capability in comparison to a totipotent cell.

[0045] The terms “polypeptide” or “peptide” or “amino acid sequence” refer to an oligopeptide, peptide, polypeptide or protein sequence or fragment thereof and to naturally occurring or synthetic molecules. A polypeptide “fragment,” “portion,” or “segment” is a stretch of amino acid residues of at least about 5 amino acids, preferably at least about 7 amino acids, more preferably at least about 9 amino acids and most preferably at least about 17 or more amino acids. The peptide preferably is not greater than about 200 amino acids, more preferably less than 150 amino acids and most preferably less than 100 amino acids. Preferably the peptide is from about 5 to about 200 amino acids. To be active, any polypeptide must have sufficient length to display biological and/or immunological activity.

[0046] The term “naturally occurring polypeptide” refers to polypeptides produced by cells that have not been genetically engineered and specifically contemplates various polypeptides arising from post-translational modifications of the polypeptide including, but not limited to, acetylation, carboxylation, glycosylation, phosphorylation, lipidation and acylation.

[0047] The term “translated protein coding portion” means a sequence which encodes for the full length protein which may include any leader sequence or any processing sequence.

[0048] The term “mature protein coding sequence” means a sequence which encodes a peptide or protein without a signal or leader sequence. The peptide may have been produced by processing in the cell which removes any leader/signal sequence. The peptide may be produced synthetically or the protein may have been produced using a polynucleotide only encoding for the mature protein coding sequence.

[0049] The term “derivative” refers to polypeptides chemically modified by such techniques as ubiquitination, labeling (e.g., with radionuclides or various enzymes), covalent polymer attachment such as pegylation (derivatization with polyethylene glycol) and insertion or substitution by chemical synthesis of amino acids such as omithine, which do not normally occur in human proteins.

[0050] The term “variant”(or “analog”) refers to any polypeptide differing from naturally occurring polypeptides by amino acid insertions, deletions, and substitutions, created using, e g., recombinant DNA techniques. Guidance in determining which amino acid residues may be replaced, added or deleted without abolishing activities of interest, may be found by comparing the sequence of the particular polypeptide with that of homologous peptides and minimizing the number of amino acid sequence changes made in regions of high homology (conserved regions) or by replacing amino acids with consensus sequence.

[0051] Alternatively, recombinant variants encoding these same or similar polypeptides may be synthesized or selected by making use of the “redundancy” in the genetic code. Various codon substitutions, such as the silent changes which produce various restriction sites, may be introduced to optimize cloning into a plasmid or viral vector or expression in a particular prokaryotic or eukaryotic system. Mutations in the polynucleotide sequence may be reflected in the polypeptide or domains of other peptides added to the polypeptide to modify the properties of any part of the polypeptide, to change characteristics such as ligand-binding affinities, interchain affinities, or degradation/turnover rate.

[0052] Preferably, amino acid “substitutions” are the result of replacing one amino acid with another amino acid having similar structural and/or chemical properties, i.e., conservative amino acid replacements. “Conservative” amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved. For example, nonpolar hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid. “Insertions” or “deletions” are preferably in the range of about 1 to 20 amino acids, more preferably 1 to 10 amino acids. The variation allowed may be experimentally determined by systematically making insertions, deletions, or substitutions of amino acids in a polypeptide molecule using recombinant DNA techniques and assaying the resulting recombinant variants for activity.

[0053] Alternatively, where alteration of function is desired, insertions, deletions or non-conservative alterations can be engineered to produce altered polypeptides. Such alterations can, for example, alter one or more of the biological functions or biochemical characteristics of the polypeptides of the invention. For example, such alterations may change polypeptide characteristics such as ligand-binding affinities, interchain affinities, or degradation/turnover rate. Further, such alterations can be selected so as to generate polypeptides that are better suited for expression, scale up and the like in the host cells chosen for expression. For example, cysteine residues can be deleted or substituted with another amino acid residue in order to eliminate disulfide bridges.

[0054] The terms “purified” or “substantially purified” as used herein denotes that the indicated nucleic acid or polypeptide is present in the substantial absence of other biological macromolecules, e.g., polynucleotides, proteins, and the like. In one embodiment, the polynucleotide or polypeptide is purified such that it constitutes at least 95% by weight, more preferably at least 99% by weight, of the indicated biological macromolecules present (but water, buffers, and other small molecules, especially molecules having a molecular weight of less than 1000 daltons, can be present).

[0055] The term “isolated” as used herein refers to a nucleic acid or polypeptide separated from at least one other component (e.g., nucleic acid or polypeptide) present with the nucleic acid or polypeptide in its natural source. In one embodiment, the nucleic acid or polypeptide is found in the presence of (if anything) only a solvent, buffer, ion, or other component normally present in a solution of the same. The terms “isolated” and “purified” do not encompass nucleic acids or polypeptides present in their natural source.

[0056] The term “recombinant,” when used herein to refer to a polypeptide or protein, means that a polypeptide or protein is derived from recombinant (e.g., microbial, insect, or mammalian) expression systems. “Microbial” refers to recombinant polypeptides or proteins made in bacterial or fungal (e.g., yeast) expression systems. As a product, “recombinant microbial” defines a polypeptide or protein essentially free of native endogenous substances and unaccompanied by associated native glycosylation. Polypeptides or proteins expressed in most bacterial cultures, e.g., E. coli, will be free of glycosylation modifications; polypeptides or proteins expressed in yeast will have a glycosylation pattern in general different from those expressed in mammalian cells.

[0057] The term “recombinant expression vehicle or vector” refers to a plasmid or phage or virus or vector, for expressing a polypeptide from a DNA (RNA) sequence. An expression vehicle can comprise a transcriptional unit comprising an assembly of (1) a genetic element or elements having a regulatory role in gene expression, for example, promoters or enhancers, (2) a structural or coding sequence which is transcribed into mRNA and translated into protein, and (3) appropriate transcription initiation and termination sequences. Strictural units intended for use in yeast or eukaryotic expression systems preferably include a leader sequence enabling extracellular secretion of translated protein by a host cell. Alternatively, where recombinant protein is expressed without a leader or transport sequence, it may include an amino terminal methionine residue. This residue may or may not be subsequently cleaved from the expressed recombinant protein to provide a final product.

[0058] The term “recombinant expression system” means host cells which have stably integrated a recombinant transcriptional unit into chromosomal DNA or carry the recombinant transcriptional unit extrachromosomally. Recombinant expression systems as defined herein will express heterologous polypeptides or proteins upon induction of the regulatory elements linked to the DNA segment or synthetic gene to be expressed. This term also means host cells which have stably integrated a recombinant genetic element or elements having a regulatory role in gene expression, for example, promoters or enhancers. Recombinant expression systems as defined herein will express polypeptides or proteins endogenous to the cell upon induction of the regulatory elements linked to the endogenous DNA segment or gene to be expressed. The cells can be prokaryotic or eukaryotic.

[0059] The term “secreted” includes a protein that is transported across or through a membrane, including transport as a result of signal sequences in its amino acid sequence when it is expressed in a suitable host cell. “Secreted” proteins include without limitation proteins secreted wholly (e.g., soluble proteins) or partially (e.g., receptors) from the cell in which they are expressed. “Secreted” proteins also include without limitation proteins that are transported across the membrane of the endoplasmic reticulum. “Secreted” proteins are also intended to include proteins containing non-typical signal sequences (e.g. Interleukin-1 Beta, see Krasney, P. A. and Young, P. R. (1992) Cytokine 4(2):134-143) and factors released from damaged cells (e.g. Interleukin- 1 Receptor Antagonist, see Arend, W. P. et. al. (1998) Annu. Rev. Immunol. 16:27-55)

[0060] Where desired, an expression vector may be designed to contain a “signal or leader sequence” which will direct the polypeptide through the membrane of a cell. Such a sequence may be naturally present on the polypeptides of the present invention or provided from heterologous protein sources by recombinant DNA techniques.

[0061] The term “stringent” is used to refer to conditions that are commonly understood in the art as stringent. Stringent conditions can include highly stringent conditions (i.e., hybridization to filter-bound DNA in 0.5 M NaHPO₄, 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C., and washing in 0.1× SSC/0.1% SDS at 68° C.), and moderately stringent conditions (i.e., washing in 0.2× SSC/0.1% SDS at 42° C.). Other exemplary hybridization conditions are described herein in the examples.

[0062] In instances of hybridization of deoxyoligonucleotides, additional exemplary stringent hybridization conditions include washing in 6× SSC/0.05% sodium pyrophosphate at 37° C. (for 14-base oligonucleotides), 48° C. (for 17-base oligos), 55° C. (for 20-base oligonucleotides), and 60° C. (for 23-base oligonucleotides).

[0063] As used herein, “substantially equivalent” can refer both to nucleotide and amino acid sequences, for example a mutant sequence, that varies from a reference sequence by one or more substitutions, deletions, or additions, the net effect of which does not result in an adverse functional dissimilarity between the reference and subject sequences. Typically, such a substantially equivalent sequence varies from one of those listed herein by no more than about 35% (i.e., the number of individual residue substitutions, additions, and/or deletions in a substantially equivalent sequence, as compared to the corresponding reference sequence, divided by the total number of residues in the substantially equivalent sequence is about 0.35 or less). Such a sequence is said to have 65% sequence identity to the listed sequence. In one embodiment, a substantially equivalent, e.g., mutant, sequence of the invention varies from a listed sequence by no more than 30% (70% sequence identity); in a variation of this embodiment, by no more than 25% (75% sequence identity); and in a further variation of this embodiment, by no more than 20% (80% sequence identity) and in a further variation of this embodiment, by no more than 10% (90% sequence identity) and in a further variation of this embodiment, by no more that 5% (95% sequence identity). Substantially equivalent, e.g., mutant, amino acid sequences according to the invention preferably have at least 80% sequence identity with a listed amino acid sequence, more preferably at least 90% sequence identity. Substantially equivalent nucleotide sequences of the invention can have lower percent sequence identities, talking into account, for example, the redundancy or degeneracy of the genetic code. Preferably, nucleotide sequence has at least about 65% identity, more preferably at least about 75% identity, and most preferably at least about 95% identity. For the purposes of the present invention, sequences having substantially equivalent biological activity and substantially equivalent expression characteristics are considered substantially equivalent. For the purposes of determining equivalence, truncation of the mature sequence (e.g., via a mutation which creates a spurious stop codon) should be disregarded. Sequence identity may be determined, e.g., using the Jotun Hein method (Hein, J. (1990) Methods Enzymol. 183:626-645). Identity between sequences can also be determined by other methods known in the art, e.g. by varying hybridization conditions.

[0064] The term “totipotent” refers to the capability of a cell to differentiate into all of the cell types of an adult organism.

[0065] The term “transformation” means introducing DNA into a suitable host cell so that the DNA is replicable, either as an extrachromosomal element, or by chromosomal integration. The term “transfection” refers to the taking up of an expression vector by a suitable host cell, whether or not any coding sequences are in fact expressed. The term “infection” refers to the introduction of nucleic acids into a suitable host cell by use of a virus or viral vector.

[0066] As used herein, an “uptake modulating fragment,” UTMF, means a series of nucleotides which mediate the uptake of a linked DNA fragment into a cell. UMFs can be readily identified using known UMFs as a target sequence or target motif with the computer-based systems described below. The presence and activity of a UMF can be confirmed by attaching the suspected UMF to a marker sequence. The resulting nucleic acid molecule is then incubated with an appropriate host under appropriate conditions and the uptake of the marker sequence is determined. As described above, a UMF will increase the frequency of uptake of a linked marker sequence.

[0067] Each of the above terms is meant to encompass all that is described for each, unless the context dictates otherwise.

NUCLEIC ACIDS OF THE INVENTION

[0068] Nucleotide sequences of the invention are set forth in the Sequence Listing.

[0069] The isolated polynucleotides of the invention include a polynucleotide comprising the nucleotide sequences of SEQ ID NO: 1-91; a polynucleotide encoding any one of the peptide sequences of SEQ ID NO: 1-91; and a polynucleotide comprising the nucleotide sequence encoding the mature protein coding sequence of the polynucleotides of any one of SEQ ID NO: 1-91. The polynucleotides of the present invention also include, but are not limited to, a polynucleotide that hybridizes under stringent conditions to (a) the complement of any of the nucleotides sequences of SEQ ID NO: 1-91; (b) nucleotide sequences encoding any one of the amino acid sequences set forth in the Sequence Listing; (c) a polynucleotide which is an allelic variant of any polynucleotide recited above; (d) a polynucleotide which encodes a species homolog of any of the proteins recited above; or (e) a polynucleotide that encodes a polypeptide comprising a specific domain or truncation of the polypeptides of SEQ ID NO: 1-91. Domains of interest may depend on the nature of the encoded polypeptide; e.g., domains in receptorlike polypeptides include ligand-binding, extracellular, transmembrane, or cytoplasmic domains, or combinations thereof; domains in immunoglobulin-like proteins include the variable immunoglobulin-like domains; domains in enzyme-like polypeptides include catalytic and substrate binding domains; and domains in ligand polypeptides include receptor-binding domains.

[0070] The polynucleotides of the invention include naturally occurring or wholly or partially synthetic DNA, e.g., cDNA and genomic DNA, and RNA, e.g., MRNA. The polynucleotides may include all of the coding region of the cDNA or may represent a portion of the coding region of the cDNA.

[0071] The present invention also provides genes corresponding to the cDNA sequences disclosed herein. The corresponding genes can be isolated in accordance with known methods using the sequence information disclosed herein. Such methods include the preparation of probes or primers from the disclosed sequence information for identification and/or amplification of genes in appropriate genomic libraries or other sources of genomic materials. Further 5′ and 3′ sequence can be obtained using methods known in the art. For example, fall length cDNA or genomric DNA that corresponds to any of the polynucleotides of SEQ ID NO: 1-91 can be obtained by screening appropriate cDNA or genomic DNA libraries under suitable hybridization conditions using any of the polynucleotides of SEQ ID NO: 1-91 or a portion thereof as a probe. Alternatively, the polynucleotides of SEQ ID NO: 1-91 may be used as the basis for suitable primer(s) that allow identification and/or amplification of genes in appropriate genomic DNA or cDNA libraries.

[0072] The nucleic acid sequences of the invention can be assembled from ESTs and sequences (including cDNA and genomic sequences) obtained from one or more public databases, such as dbEST, gbpri, and UniGene. The EST sequences can provide identifying sequence information, representative fragment or segment information, or novel segment information for the full-length gene.

[0073] The polynucleotides of the invention also provide polynucleotides including nucleotide sequences that are substantially equivalent to the polynucleotides recited above. Polynucleotides according to the invention can have, e.g., at least about 65%, at least about 70%, at least about 75%, at least about 80%, more typically at least about 90%, and even more typically at least about 95%, sequence identity to a polynucleotide recited above.

[0074] Included within the scope of the nucleic acid sequences of the invention are nucleic acid sequence fragments that hybridize under stringent conditions to any of the nucleotide sequences of SEQ ID NO: 1-91, or complements thereof, which fragment is greater than about 5 nucleotides, preferably 7 nucleotides, more preferably greater than 9 nucleotides and most preferably greater than 17 nucleotides. Fragments of, e.g. 15, 17, or 20 nucleotides or more that are selective for (i.e. specifically hybridize to any one of the polynucleotides of the invention) are contemplated. Probes capable of specifically hybridizing to a polynucleotide can differentiate polynucleotide sequences of the invention from other polynucleotide sequences in the same family of genes or can differentiate human genes from genes of other species, and are preferably based on unique nucleotide sequences.

[0075] The sequences falling within the scope of the present invention are not limited to these specific sequences, but also include allelic and species variations thereof. Allelic and species variations can be routinely determined by comparing the sequence provided in SEQ ID NO: 1-91, a representative fragment thereof, or a nucleotide sequence at least 90% identical, preferably 95% identical, to SEQ ID NOs: 1-91 with a sequence from another isolate of the same species. Furthermore, to accommodate codon variability, the invention includes nucleic acid molecules coding for the same amino acid sequences as do the specific ORFs disclosed herein. In other words, in the coding region of an ORF, substitution of one codon for another codon that encodes the same amino acid is expressly contemplated.

[0076] The nearest neighbor or homology result for the nucleic acids of the present invention, including SEQ ID NOs: 1-91, can be obtained by searching a database using an algorithm or a program. Preferably, a BLAST which stands for Basic Local Alignment Search Tool is used to search for local sequence alignments (Altshul, S. F. J Mol. Evol. 36 290-300 (1993) and Altschul S. F. et al. J. Mol. Biol. 21:403-410 (1990)). Alternatively a FASTA version 3 search against Genpept, using Fastxy algorithm.

[0077] Species homologs (or orthologs) of the disclosed polynucleotides and proteins are also provided by the present invention. Species homologs may be isolated and identified by making suitable probes or primers from the sequences provided herein and screening a suitable nucleic acid source from the desired species.

[0078] The invention also encompasses allelic variants of the disclosed polynucleotides or proteins; that is, naturally-occurring alternative forms of the isolated polynucleotide which also encode proteins which are identical, homologous or related to that encoded by the polynucleotides.

[0079] The nucleic acid sequences of the invention are further directed to sequences which encode variants of the described nucleic acids. These amino acid sequence variants may be prepared by methods known in the art by introducing appropriate nucleotide changes into a native or variant polynucleotide. There are two variables in the construction of amino acid sequence variants: the location of the mutation and the nature of the mutation. Nucleic acids encoding the amino acid sequence variants are preferably constructed by mutating the polynucleotide to encode an amino acid sequence that does not occur in nature. These nucleic acid alterations can be made at sites that differ in the nucleic acids from different species (variable positions) or in highly conserved regions (constant regions). Sites at such locations will typically be modified in series, e.g., by substituting first with conservative choices (e.g., hydrophobic amino acid to a different hydrophobic amino acid) and then with more distant choices (e.g., hydrophobic amino acid to a charged amino acid), and then deletions or insertions may be made at the target site. Amino acid sequence deletions generally range from about 1 to 30 residues, preferably about 1 to 10 residues, and are typically contiguous. Amino acid insertions include amino- and/or carboxyl-terminal fusions ranging in length from one to one hundred or more residues, as well as intrasequence insertions of single or multiple amino acid residues. Intrasequence insertions may range generally from about 1 to 10 amino residues, preferably from 1 to 5 residues. Examples of terminal insertions include the heterologous signal sequences necessary for secretion or for intracellular targeting in different host cells and sequences such as FLAG or poly-histidine sequences useful for purifying the expressed protein.

[0080] In a preferred method, polynucleotides encoding the novel amino acid sequences are changed via site-directed mutagenesis. This method uses oligonucleotide sequences to alter a polynucleotide to encode the desired amino acid variant, as well as sufficient adjacent nucleotides on both sides of the changed amino acid to form a stable duplex on either side of the site of being changed. In general, the techniques of site-directed mutagenesis are well known to those of skill in the art and this technique is exemplified by publications such as, Edelman et al., DNA 2:183 (1983). A versatile and efficient method for producing site-specific changes in a polynucleotide sequence was published by Zoller and Smith, Nucleic Acids Res. 10:6487-6500 (1982). PCR may also be used to create amino acid sequence variants of the novel nucleic acids. When small amounts of template DNA are used as starting material, primer(s) that differs slightly in sequence from the corresponding region in the template DNA can generate the desired amino acid variant. PCR amplification results in apopulation of product DNA fragments that differ from the polynucleotide template encoding the polypeptide at the position specified by the primer. The product DNA fragments replace the corresponding region in the plasmid and this gives a polynucleotide encoding the desired amino acid variant.

[0081] A further technique for generating amino acid variants is the cassette mutagenesis technique described in Wells et al., Gene 34:315 (1985); and other mutagenesis techniques well known in the art, such as, for example, the techniques in Sambrook et al., supra, and Current Protocols in Molecular Biology, Ausubel et al. Due to the inherent degeneracy of the genetic code, other DNA sequences which encode substantially the same or a functionally equivalent amino acid sequence may be used in the practice of the invention for the cloning and expression of these novel nucleic acids. Such DNA sequences include those which are capable of hybridizing to the appropriate novel nucleic acid sequence under stringent conditions.

[0082] Polynucleotides encoding preferred polypeptide trincations of the invention can be used to generate polynucleotides encoding chimeric or fusion proteins comprising one or more domains of the invention and heterologous protein sequences.

[0083] The polynucleotides of the invention additionally include the complement of any of the polynucleotides recited above. The polynucleotide can be DNA (genomic, cDNA, amplified, or synthetic) or RNA. Methods and algorithms for obtaining such polynucleotides are well known to those of skill in the art and can include, for example, methods for determining hybridization conditions that can routinely isolate polynucleotides of the desired sequence identities.

[0084] In accordance with the invention, polynucleotide sequences comprising the mature protein coding sequences corresponding to any one of SEQ ID NO: 1-91, or functional equivalents thereof, may be used to generate recombinant DNA molecules that direct the expression of that nucleic acid, or a functional equivalent thereof, in appropriate host cells. Also included are the cDNA inserts of any of the clones identified herein.

[0085] A polynucleotide according to the invention can be joined to any of a variety of other nucleotide sequences by well-established recombinant DNA techniques (see Sambrook J et al. (1989) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, N.Y.). Useful nucleotide sequences for joining to polynucleotides include an assortment of vectors, e.g., plasmids, cosmids, lambda phage derivatives, phagemids, and the like, that are well known in the art. Accordingly, the invention also provides a vector including a polynucleotide of the invention and a host cell containing the polynucleotide. In general, the vector contains an origin of replication functional in at least one organism, convenient restriction endonuclease sites, and a selectable marker for the host cell. Vectors according to the invention include expression vectors, replication vectors, probe generation vectors, and sequencing vectors. A host cell according to the invention can be a prokaryotic or eukaryotic cell and can be a unicellular organism or part of a multicellular organism.

[0086] The present invention further provides recombinant constructs comprising a nucleic acid having any of the nucleotide sequences of SEQ ID NOs: 1-91 or a fragment thereof or any other polynucleotides of the invention. In one embodiment, the recombinant constructs of the present invention comprise a vector, such as a plasmid or viral vector, into which a nucleic acid having any of the nucleotide sequences of SEQ ID NOs: 1-91 or a fragment thereof is inserted, in a forward or reverse orientation. In the case of a vector comprising one of the ORFs of the present invention, the vector may further comprise regulatory sequences, including for example, a promoter, operably linked to the ORF. Large numbers of suitable vectors and promoters are known to those of skill in the art and are commercially available for generating the recombinant constructs of the present invention. The following vectors are provided by way of example. Bacterial: pBs, phagescript, PsiX174, pbluescript SK, pBs KS, pNH8a, pNH16a, pNH18a, pNH46a (Stratagene); pTrc99A, pKK223-3, pKK233-3, pDR540, pRIT5 (Phan-nacia). Eukaryotic: pWLneo, pSV2cat, pOG44, PXTI, pSG (Stratagene) pSVK3, pBPV, pMSG, pSVL (Pharnacia).

[0087] The isolated polynucleotide of the invention may be operably linked to an expression control sequence such as the pMT2 or pED expression vectors disclosed in Kaufrnan et al., Nucleic Acids Res. 19, 4485-4490 (1991), in order to produce the protein recombinantly. Many suitable expression control sequences are known in the art. General methods of expressing recombinant proteins are also known and are exemplified in R. Kaufmnan, Methods in Enzymology 185, 537-566 (1990). As defined herein “operably linked” means that the isolated polynucleotide of the invention and an expression control sequence are situated within a vector or cell in such a way that the protein is expressed by a host cell which has been transformed (transfected) with the ligated polynucleotide/expression control sequence.

[0088] Promoter regions can be selected from any desired gene using CAT (chloramphenicol transferase) vectors or other vectors with selectable markers. Two appropriate vectors are pKK232-8 and pCM7. Particular named bacterial promoters include lacI, lacZ, T3, T7, gpt, lambda PR, and trc. Eukaryotic promoters include CMV immediate early, HSV thymidine kinase, early and late SV40, LTRs from retrovirus, and mouse metallothionein-I. Selection of the appropriate vector and promoter is well within the level of ordinary skill in the art. Generally, recombinant expression vectors will include origins of replication and selectable markers permitting transformation of the host cell, e.g., the ampicillin resistance gene of E. coli and S. cerevisiae TRP1 gene, and a promoter derived from a highly-expressed gene to direct transcription of a downstream structural sequence. Such promoters can be derived from operons encoding glycolytic enzymes such as 3-phosphoglycerate kinase (PGK), a-factor, acid phosphatase, or heat shock proteins, among others. The heterologous structural sequence is assembled in appropriate phase with translation initiation and termination sequences, and preferably, a leader sequence capable of directing secretion of translated protein into the periplasmic space or extracellular medium. Optionally, the heterologous sequence can encode a fusion protein including an amino terminal identification peptide imparting desired characteristics, e.g., stabilization or simplified purification of expressed recombinant product. Useful expression vectors for bacterial use are constructed by inserting a structural DNA sequence encoding a desired protein together with suitable translation initiation and termination signals in operable reading phase with a functional promoter. The vector will comprise one or more phenotypic selectable markers and an origin of replication to ensure maintenance of the vector and to, if desirable, provide amplification within the host. Suitable prokaryotic hosts for transformation include E. coli, Bacillus subtilis, Salmonella typhimurium and various species within the genera Pseudomonas, Streptomyces, and Staphylococcus, although others may also be employed as a matter of choice.

[0089] As a representative but non-limiting example, useful expression vectors for bacterial use can comprise a selectable marker and bacterial origin of replication derived from commercially available plasmids comprising genetic elements of the well known cloning vector pBR322 (ATCC 37017). Such commercial vectors include, for example, pKK223-3 (Pharmacia Fine Chemicals, Uppsala, Sweden) and GEM 1 (Promega Biotech, Madison, Wis., USA). These pBR322 “backbone” sections are combined with an appropriate promoter and the structural sequence to be expressed. Following transformation of a suitable host strain and growth of the host strain to an appropriate cell density, the selected promoter is induced or derepressed by appropriate means (e.g., temperature shift or chemical induction) and cells are cultured for an additional period. Cells are typically harvested by centrifugation, disrupted by physical or chemical means, and the resulting crude extract retained for further purification.

[0090] Polynucleotides of the invention can also be used to induce immune responses. For example, as described in Fan et al., Nat. Biotech. 17:870-872 (1999), incorporated herein by reference, nucleic acid sequences encoding a polypeptide may be used to generate antibodies against the encoded polypeptide following topical administration of naked plasmid DNA or following injection, and preferably intramuscular injection of the DNA. The nucleic acid sequences are preferably inserted in a recombinant expression vector and may be in the form of naked DNA.

HOSTS

[0091] The present invention further provides host cells genetically engineered to contain the polynucleotides of the invention. For example, such host cells may contain nucleic acids of the invention introduced into the host cell using known transformation, transfection or infection methods. The present invention still further provides host cells genetically engineered to express the polynucleotides of the invention, wherein such polynucleotides are in operative association with a regulatory sequence heterologous to the host cell which drives expression of the polynucleotides in the cell.

[0092] Knowledge of nucleic acid sequences allows for modification of cells to permit, or increase, expression of endogenous polypeptide. Cells can be modified (e.g., by homologous recombination) to provide increased polypeptide expression by replacing, in whole or in part, the naturally occurring promoter with all or part of a heterologous promoter so that the cells express the polypeptide at higher levels. The heterologous promoter is inserted in such a manner that it is operatively linked to the encoding sequences. See, for example, PCT International Publication No. WO94/12650, PCT International Publication No. WO92/20808, and PCT International Publication No. WO91/09955. It is also contemplated that, in addition to heterologous promoter DNA, amplifiable marker DNA (e.g., ada, dhfr, and the multifunctional CAD gene which encodes carbamyl phosphate synthase, aspartate transcarbamylase, and dihydroorotase) and/or intron DNA may be inserted along with the heterologous promoter DNA. If linked to the coding sequence, amplification of the marker DNA by standard selection methods results in co-amplification of the desired protein coding sequences in the cells.

[0093] The host cell can be a higher eukaryotic host cell, such as a mammalian cell, a lower eukaryotic host cell, such as a yeast cell, or the host cell can be a prokaryotic cell, such as a bacterial cell. Introduction of the recombinant construct into the host cell can be effected by calcium phosphate transfection, DEAE, dextran mediated transfection, or electroporation (Davis, L. et al., Basic Methods in Molecular Biology (1986)). The host cells containing one of the polynucleotides of the invention, can be used in conventional manners to produce the gene product encoded by the isolated fragment (in the case of an ORF) or can be used to produce a heterologous protein under the control of the EMF.

[0094] Any host/vector system can be used to express one or more of the OR-s of the present invention. These include, but are not limited to, eukaryotic hosts such as HeLa cells, Cv-1 cell, COS cells, 293 cells, and Sf9 cells, as well as prokaryotic host such as E. coli and B. subtilis. The most preferred cells are those which do not normally express the particular polypeptide or protein or which expresses the polypeptide or protein at low natural level. Mature proteins can be expressed in mammalian cells, yeast, bacteria, or other cells under the control of appropriate promoters. Cell-free translation systems can also be employed to produce such proteins using RNAs derived from the DNA constructs of the present invention. Appropriate cloning and expression vectors for use with prokaryotic and eukaryotic hosts are described by Sambrook, et al., in Molecular Cloning: A Laboratory Manual, Second Edition, Cold Spring Harbor, N.Y. (1989), the disclosure of which is hereby incorporated by reference.

[0095] Various mammalian cell culture systems can also be employed to express recombinant protein. Examples of mammalian expression systems include the COS-7 lines of monkey kidney fibroblasts, described by Gluzman, Cell 23:175 (1981). Other cell lines capable of expressing a compatible vector are, for example, the C127, monkey COS cells, Chinese Hamster Ovary (CHO) cells, human kidney 293 cells, human epidermal A431 cells, human Colo205 cells, 3T3 cells, CV-1 cells, other transformed primate cell lines, normal diploid cells, cell strains derived from in vitro culture of primary tissue, primary explants, HeLa cells, mouse L cells, BHK, HL-60, U937, HaK or Jurkat cells. Mammalian expression vectors will comprise an origin of replication, a suitable promoter and also any necessary ribosome binding sites, polyadenylation site, splice donor and acceptor sites, transcriptional termination sequences, and 5′ flanking nontranscribed sequences. DNA sequences derived from the SV40 viral genome, for example, SV40 origin, early promoter, enhancer, splice, and polyadenylation sites may be used to provide the required nontranscribed genetic elements. Recombinant polypeptides and proteins produced in bacterial culture are usually isolated by initial extraction from cell pellets, followed by one or more salting-out, aqueous ion exchange or size exclusion chromatography steps. Protein refolding steps can be used, as necessary, in completing configuration of the mature protein. Finally, high performance liquid chromatography (HPLC) can be employed for final purification steps. Microbial cells employed in expression of proteins can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents.

[0096] Alternatively, it may be possible to produce the protein in lower eukaryotes such as yeast or insects or in prokaryotes such as bacteria. Potentially suitable yeast strains include Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces strains, Candida, or any yeast strain capable of expressing heterologous proteins. Potentially suitable bacterial strains include Escherichia coli, Bacillus subtilis, Salmonella typhimurium, or any bacterial strain capable of expressing heterologous proteins. If the protein is made in yeast or bacteria, it may be necessary to modify the protein produced therein, for example by phosphorylation or glycosylation of the appropriate sites, in order to obtain the functional protein. Such covalent attachments may be accomplished using known chemical or enzymatic methods.

[0097] In another embodiment of the present invention, cells and tissues may be engineered to express an endogenous gene comprising the polynucleotides of the invention under the control of inducible regulatory elements, in which case the regulatory sequences of the endogenous gene may be replaced by homologous recombination. As described herein, gene targeting can be used to replace a gene's existing regulatory region with a regulatory sequence isolated from a different gene or a novel regulatory sequence synthesized by genetic engineering methods. Such regulatory sequences may be comprised of promoters, enhancers, scaffold-attachment regions, negative regulatory elements, transcriptional initiation sites, regulatory protein binding sites or combinations of said sequences. Alternatively, sequences which affect the structure or stability of the RNA or protein produced may be replaced, removed, added, or otherwise modified by targeting. These sequence include polyadenylation signals, mRNA stability elements, splice sites, leader sequences for enhancing or modifying transport or secretion properties of the protein, or other sequences which alter or improve the function or stability of protein or RNA molecules.

[0098] The targeting event may be a simple insertion of the regulatory sequence, placing the gene under the control of the new regulatory sequence, e.g., inserting a new promoter or enhancer or both upstream of a gene. Alternatively, the targeting event may be a simple deletion of a regulatory element, such as the deletion of a tissue-specific negative regulatory element. Alternatively, the targeting event may replace an existing element; for example, a tissue-specific enhancer can be replaced by an enhancer that has broader or different cell-type specificity than the naturally occurring elements. Here, the naturally occurring sequences are deleted and new sequences are added. In all cases, the identification of the targeting event may be facilitated by the use of one or more selectable marker genes that are contiguous with the targeting DNA, allowing for the selection of cells in which the exogenous DNA has integrated into the host cell genome. The identification of the targeting event may also be facilitated by the use of one or more marker genes exhibiting the property of negative selection, such that the negatively selectable marker is linked to the exogenous DNA, but configured such that the negatively selectable marker flanks the targeting sequence, and such that a correct homologous recombination event with sequences in the host cell genome does not result in the stable integration of the negatively selectable marker. Markers useful for this purpose include the Herpes Simplex Virus thymidine kinase (TK) gene or the bacterial xanthine-guanine phosphoribosyl-transferase (gpt) gene.

[0099] The gene targeting or gene activation techniques which can be used in accordance with this aspect of the invention are more particularly described in U.S. Pat. No. 5,272,071 to Chappel; U.S. Pat. No. 5,578,461 to Sherwin et al.; International Application No. PCT/US92/09627 (WO93/09222) by Selden et al.; and International Application No. PCT/US90/06436 (WO91/06667) by Skoultchi et al., each of which is incorporated by reference herein in its entirety.

POLYPEPTIDES OF THE INVENTION

[0100] The isolated polypeptides of the invention include, but are not limited to, a polypeptide comprising: the amino acid sequences set forth as any one of SEQ ID NO: 1-91 or an amino acid sequence encoded by any one of the nucleotide sequences SEQ ID NOs: 1-91 or the corresponding fall length or mature protein. Polypeptides of the invention also include polypeptides preferably with biological or immunological activity that are encoded by: (a) a polynucleotide having any one of the nucleotide sequences set forth in SEQ ID NOs: 1-91 or (b) polynucleotides encoding any one of the amino acid sequences set forth as SEQ ID NO: 1-91 or (c) polynucleotides that hybridize to the complement of the polynucleotides of either (a) or (b) under stringent hybridization conditions. The invention also provides biologically active or immunologically active variants of any of the amino acid sequences set forth as SEQ ID NO: 1-91 or the corresponding fall length or mature protein; and “substantial equivalents” thereof (e.g., with at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, typically at least about 95%, more typically at least about 98%, or most typically at least about 99% amino acid identity) that retain biological activity. Polypeptides encoded by allelic variants may have a similar, increased, or decreased activity compared to polypeptides comprising SEQ ID NO: 1-91.

[0101] Fragments of the proteins of the present invention which are capable of exhibiting biological activity are also encompassed by the present invention. Fragments of the protein may be in linear form or they may be cyclized using known methods, for example, as described in H. U. Saragovi, et al., Bio/Technology 10, 773-778 (1992) and in R. S. McDowell, et al., J. Amer. Chem. Soc. 114, 9245-9253 (1992), both of which are incorporated herein by reference. Such fragments may be fused to carrier molecules such as immunoglobulins for many purposes, including increasing the valency of protein binding sites.

[0102] The present invention also provides both full-length and mature forms (for example, without a signal sequence or precursor sequence) of the disclosed proteins. The protein coding sequence is identified in the sequence listing by translation of the disclosed nucleotide sequences. The mature form of such protein may be obtained by expression of a full-length polynucleotide in a suitable mammalian cell or other host cell. The sequence of the mature form of the protein is also determinable from the amino acid sequence of the full-length form. Where proteins of the present invention are membrane bound, soluble forms of the proteins are also provided. In such forms, part or all of the regions causing the proteins to be membrane bound are deleted so that the proteins are fully secreted from the cell in which it is expressed.

[0103] Protein compositions of the present invention may further comprise an acceptable carrier, such as a hydrophilic, e.g., pharmaceutically acceptable, carrier.

[0104] The present invention further provides isolated polypeptides encoded by the nucleic acid fragments of the present invention or by degenerate variants of the nucleic acid fragments of the present invention. By “degenerate variant” is intended nucleotide fragments which differ from a nucleic acid fragment of the present invention (e.g., an ORF) by nucleotide sequence but, due to the degeneracy of the genetic code, encode an identical polypeptide sequence. Preferred nucleic acid fragments of the present invention are the ORFs that encode proteins.

[0105] A variety of methodologies known in the art can be utilized to obtain any one of the isolated polypeptides or proteins of the present invention. At the simplest level, the amino acid sequence can be synthesized using commercially available peptide synthesizers. The synthetically-constructed protein sequences, by virtue of sharing primary, secondary or tertiary structural and/or conformational characteristics with proteins may possess biological properties in common therewith, including protein activity. This technique is particularly useful in producing small peptides and fragments of larger polypeptides. Fragments are useful, for example, in generating antibodies against the native polypeptide. Thus, they may be employed as biologically active or immunological substitutes for natural, purified proteins in screening of therapeutic compounds and in immunological processes for the development of antibodies.

[0106] The polypeptides and proteins of the present invention can alternatively be purified from cells which have been altered to express the desired polypeptide or protein. As used herein, a cell is said to be altered to express a desired polypeptide or protein when the cell, through genetic manipulation, is made to produce a polypeptide or protein which it normally does not produce or which the cell normally produces at a lower level. One skilled in the art can readily adapt procedures for introducing and expressing either recombinant or synthetic sequences into eukaryotic or prokaryotic cells in order to generate a cell which produces one of the polypeptides or proteins of the present invention.

[0107] The invention also relates to methods for producing a polypeptide comprising growing a culture of host cells of the invention in a suitable culture medium, and purifying the protein from the cells or the culture in which the cells are grown. For example, the methods of the invention include a process for producing a polypeptide in which a host cell containing a suitable expression vector that includes a polynucleotide of the invention is cultured under conditions that allow expression of the encoded polypeptide. The polypeptide can be recovered from the culture, conveniently from the culture medium, or from a lysate prepared from the host cells and further purified. Preferred embodiments include those in which the protein produced by such process is a fall length or mature form of the protein.

[0108] In an alternative method, the polypeptide or protein is purified from bacterial cells which naturally produce the polypeptide or protein. One skilled in the art can readily follow known methods for isolating polypeptides and proteins in order to obtain one of the isolated polypeptides or proteins of the present invention. These include, but are not limited to, immunochromatography, HPLC, size-exclusion chromatography, ion-exchange chromatography, and immuno-affinity chromatography. See, e.g., Scopes, Protein Purification: Principles and Practice, Springer-Verlag (1994); Sambrook, et al., in Molecular Cloning: A Laboratory Manual; Ausubel et al., Current Protocols in Molecular Biology. Polypeptide fragments that retain biological/immunological activity include fragments comprising greater than about 100 amino acids, or greater than about 200 amino acids, and fragments that encode specific protein domains.

[0109] The purified polypeptides can be used in in vitro binding assays which are well known in the art to identify molecules which bind to the polypeptides. These molecules include but are not limited to, for e.g., small molecules, molecules from combinatorial libraries, antibodies or other proteins. The molecules identified in the binding assay are then tested for antagonist or agonist activity in in vivo tissue culture or animal models that are well known in the art. In brief, the molecules are titrated into a plurality of cell cultures or animals and then tested for either cell/animal death or prolonged survival of the animal/cells.

[0110] In addition, the peptides of the invention or molecules capable of binding to the peptides may be complexed with toxins, e.g., ricin or cholera, or with other compounds that are toxic to cells. The toxin-binding molecule complex is then targeted to a tumor or other cell by the specificity of the binding molecule for SEQ ID NO: 1-91.

[0111] The protein of the invention may also be expressed as a product of transgenic animals, e.g., as a component of the milk of transgenic cows, goats, pigs, or sheep which are characterized by somatic or germ cells containing a nucleotide sequence encoding the protein.

[0112] The proteins provided herein also include proteins characterized by amino acid sequences similar to those of purified proteins but into which modification are naturally provided or deliberately engineered. For example, modifications, in the peptide or DNA sequence, can be made by those skilled in the art using known techniques. Modifications of interest in the protein sequences may include the alteration, substitution, replacement, insertion or deletion of a selected amino acid residue in the coding sequence. For example, one or more of the cysteine residues may be deleted or replaced with another amino acid to alter the conformation of the molecule. Techniques for such alteration, substitution, replacement, insertion or deletion are well known to those skilled in the art (see, e.g., U.S. Pat. No. 4,518,584). Preferably, such alteration, substitution, replacement, insertion or deletion retains the desired activity of the protein. Regions of the protein that are important for the protein function can be determined by various methods known in the art including the alanine-scanning method which involved systematic substitution of single or strings of amino acids with alanine, followed by testing the resulting alanine-containing variant for biological activity. This type of analysis determines the importance of the substituted amino acid(s) in biological activity. Regions of the protein that are important for protein function may be determined by the eMATRIX program.

[0113] Other fragments and derivatives of the sequences of proteins which would be expected to retain protein activity in whole or in part and are useful for screening or other immunological methodologies may also be easily made by those skilled in the art given the disclosures herein. Such modifications are encompassed by the present invention.

[0114] The protein may also be produced by operably linking the isolated polynucleotide of the invention to suitable control sequences in one or more insect expression vectors, and employing an insect expression system. Materials and methods for baculovirus/insect cell expression systems are commercially available in kit form from, e.g., Invitrogen, San Diego, Calif., U.S.A. (the MaxBat™ kit), and such methods are well known in the art, as described in Summers and Smith, Texas Agricultural Experiment Station Bulletin No. 1555 (1987), incorporated herein by reference. As used herein, an insect cell capable of expressing a polynucleotide of the present invention is “transformed.”

[0115] The protein of the invention may be prepared by culturing transformed host cells under culture conditions suitable to express the recombinant protein. The resulting expressed protein may then be purified from such culture (i.e., from culture medium or cell extracts) using known purification processes, such as gel filtration and ion exchange chromatography. The purification of the protein may also include an affinity column containing agents which will bind to the protein; one or more column steps over such affinity resins as concanavalin A-agarose, heparin-toyopearl™ or Cibacrom blue 3GA Sepharose™; one or more steps involving hydrophobic interaction chromatography using such resins as phenyl ether, butyl ether, or propyl ether; or immunoaffinity chromatography.

[0116] Alternatively, the protein of the invention may also be expressed in a form which will facilitate purification. For example, it may be expressed as a fusion protein, such as those of maltose binding protein (MBP), glutathione-S-transferase (GST) or thioredoxin (TRX), or as a His tag. Kits for expression and purification of such fusion proteins are commercially available from New England BioLab (Beverly, Mass.), Pharmacia (Piscataway, N.J.) and Invitrogen, respectively. The protein can also be tagged with an epitope and subsequently purified by using a specific antibody directed to such epitope. One such epitope (“FLAG®”) is commercially available from Kodak (New Haven, Conn.).

[0117] Finally, one or more reverse-phase high performance liquid chromatography (RP-HPLC) steps employing hydrophobic RP-HPLC media, e.g., silica gel having pendant methyl or other aliphatic groups, can be employed to further purify the protein. Some or all of the foregoing purification steps, in various combinations, can also be employed to provide a substantially homogeneous isolated recombinant protein. The protein thus purified is substantially free of other mammalian proteins and is defined in accordance with the present invention as an “isolated protein.”

[0118] The polypeptides of the invention include analogs (variants). This embraces fragments, as well as peptides in which one or more amino acids has been deleted, inserted, or substituted. Also, analogs of the polypeptides of the invention embrace fusions of the polypeptides or modifications of the polypeptides of the invention, wherein the polypeptide or analog is fused to another moiety or moieties, e.g., targeting moiety or another therapeutic agent. Such analogs may exhibit improved properties such as activity and/or stability. Examples of moieties which may be fused to the polypeptide or an analog include, for example, targeting moieties which provide for the delivery of polypeptide to pancreatic cells, e.g., antibodies to pancreatic cells, antibodies to immune cells such as T-cells, monocytes, dendritic cells, granulocytes, etc., as well as receptor and ligands expressed on pancreatic or immune cells. Other moieties which may be fused to the polypeptide include therapeutic agents which are used for treatment, for example, immunosuppressive drugs such as cyclosporin, SK506, azathioprine, CD3 antibodies and steroids. Also, polypeptides may be fused to immune modulators, and other cytokines such as alpha or beta interferon.

DETERMINING POLYPEPTIDE AND POLYNUCLEOTIDE IDENTITY AND SIMILARITY

[0119] Preferred identity and/or similarity are designed to give the largest match between the sequences tested. Methods to determine identity and similarity are codified in computer programs including, but are not limited to, the GCG program package, including GAP (Devereux, J., et al., Nucleic Acids Research 12(1):387 (1984); Genetics Computer Group, University of Wisconsin, Madison, Wis.), BLASTP, BLASTN, BLASTX, FASTA (Altschul, S. F. et al., J. Molec. Biol. 215:403-410 (1990), PSI-BLAST (Altschul S. F. et al., Nucleic Acids Res. vol. 25, pp. 3389-3402, herein incorporated by reference), eMatrix software (Wu et al., J. Comp. Biol., Vol. 6, pp. 219-235 (1999), herein incorporated by reference), eMotif software (Nevill-Manning et al, ISMB-97, Vol. 4, pp. 202-209, herein incorporated by reference), pFam software (Sonnhammer et al., Nucleic Acids Res., Vol. 26(1), pp. 320-322 (1998), herein incorporated by reference) and the Kyte-Doolittle hydrophobocity prediction algorithm (J. Mol Biol, 157, pp. 105-31 (1982), incorporated herein by reference). The BLAST programs are publicly available from the National Center for Biotechnology Information (NCBD) and other sources (BLAST Manual, Altschul, S., et al. NCB NLM NIH Bethesda, Md. 20894; Altschul, S., et al., J. Mol. Biol. 215:403-410 (1990).

GENE THERAPY

[0120] Mutations in the polynucleotides of the invention gene may result in loss of normal function of the encoded protein. The invention thus provides gene therapy to restore normal activity of the polypeptides of the invention; or to treat disease states involving polypeptides of the invention. Delivery of a functional gene encoding polypeptides of the invention to appropriate cells is effected ex vivo, in situ, or in vivo by use of vectors, and more particularly viral vectors (e.g., adenovirus, adeno-associated virus, or a retrovirus), or ex vivo by use of physical DNA transfer methods (e.g., liposomes or chemical treatments). See, for example, Anderson, Nature, supplement to vol. 392, no. 6679, pp.25-20 (1998). For additional reviews of gene therapy technology see Friedmann, Science, 244: 1275-1281 (1989); Verma, Scientific American: 68-84 (1990); and Miller, Nature, 357: 455-460 (1992). Introduction of any one of the nucleotides of the present invention or a gene encoding the polypeptides of the present invention can also be accomplished with extrachromosomal substrates (transient expression) or artificial chromosomes (stable expression). Cells may also be cultured ex vivo in the presence of proteins of the present invention in order to proliferate or to produce a desired effect on or activity in such cells. Treated cells can then be introduced in vivo for therapeutic purposes. Alternatively, it is contemplated that in other human disease states, preventing the expression of or inhibiting the activity of polypeptides of the invention will be useful in treating the disease states. It is contemplated that antisense therapy or gene therapy could be applied to negatively regulate the expression of polypeptides of the invention.

[0121] Other methods inhibiting expression of a protein include the introduction of antisense molecules to the nucleic acids of the present invention, their complements, or their translated RNA sequences, by methods known in the art. Further, the polypeptides of the present invention can be inhibited by using targeted deletion methods, or the insertion of a negative regulatory element such as a silencer, which is tissue specific.

[0122] The present invention still further provides cells genetically engineered in vivo to express the polynucleotides of the invention, wherein such polynucleotides are in operative association with a regulatory sequence heterologous to the host cell which drives expression of the polynucleotides in the cell. These methods can be used to increase or decrease the expression of the polynucleotides of the present invention.

[0123] Knowledge of DNA sequences provided by the invention allows for modification of cells to permit, increase, or decrease, expression of endogenous polypeptide. Cells can be modified (e.g., by homologous recombination) to provide increased polypeptide expression by replacing, in whole or in part, the naturally occurring promoter with all or part of a heterologous promoter so that the cells express the protein at higher levels. The heterologous promoter is inserted in such a manner that it is operatively linked to the desired protein encoding sequences. See, for example, PCT International Publication No. WO 94/12650, PCT International Publication No. WO 92/20808, and PCT International Publication No. WO 91/09955. It is also contemplated that, in addition to heterologous promoter DNA, ampliflable marker DNA (e.g., ada, dhfr, and the multifunctional CAD gene which encodes carbamyl phosphate synthase, aspartate transcarbamylase, and dihydroorotase) and/or intron DNA may be inserted along with the heterologous promoter DNA. If linked to the desired protein coding sequence, amplification of the marker DNA by standard selection methods results in co-amplification of the desired protein coding sequences in the cells.

[0124] In another embodiment of the present invention, cells and tissues may be engineered to express an endogenous gene comprising the polynucleotides of the invention under the control of inducible regulatory elements, in which case the regulatory sequences of the endogenous gene may be replaced by homologous recombination. As described herein, gene targeting can be used to replace a gene's existing regulatory region with a regulatory sequence isolated from a different gene or a novel regulatory sequence synthesized by genetic engineering methods. Such regulatory sequences may be comprised of promoters, enhancers, scaffold-attachment regions, negative regulatory elements, transcriptional initiation sites, regulatory protein binding sites or combinations of said sequences. Alternatively, sequences which affect the structure or stability of the RNA or protein produced may be replaced, removed, added, or otherwise modified by targeting. These sequences include polyadenylation signals, mRNA stability elements, splice sites, leader sequences for enhancing or modifying transport or secretion properties of the protein, or other sequences which alter or improve the function or stability of protein or RNA molecules.

[0125] The targeting event may be a simple insertion of the regulatory sequence, placing the gene under the control of the new regulatory sequence, e.g., inserting a new promoter or enhancer or both upstream of a gene. Alternatively, the targeting event may be a simple deletion of a regulatory element, such as the deletion of a tissue-specific negative regulatory element. Alternatively, the targeting event may replace an existing element; for example, a tissue-specific enhancer can be replaced by an enhancer that has broader or different cell-type specificity than the naturally occurring elements. Here, the naturally occurring sequences are deleted and new sequences are added. In all cases, the identification of the targeting event may be facilitated by the use of one or more selectable marker genes that are contiguous with the targeting DNA, allowing for the selection of cells in which the exogenous DNA has integrated into the cell genome. The identification of the targeting event may also be facilitated by the use of one or more marker genes exhibiting the property of negative selection, such that the negatively selectable marker is linked to the exogenous DNA, but configured such that the negatively selectable marker flanks the targeting sequence, and such that a correct homologous recombination event with sequences in the host cell genome does not result in the stable integration of the negatively selectable marker. Markers useful for this purpose include the Herpes Simplex Virus thymidine kinase (TK) gene or the bacterial xanthine-guanine phosphoribosyl-transferase (gpt) gene.

[0126] The gene targeting or gene activation techniques which can be used in accordance with this aspect of the invention are more particularly described in U.S. Pat. No. 5,272,071 to Chappel; U.S. Pat. No. 5,578,461 to Sherwin et al.; International Application No. PCT/US92/09627 (WO93/09222) by Selden et al.; and International Application No. PCT/US90/06436 (WO91/06667) by Skoultchi et al., each of which is incorporated by reference herein in its entirety.

TRANSGENIC ANIMALS

[0127] In preferred methods to determine biological functions of the polypeptides of the invention in vivo, one or more genes provided by the invention are either over expressed or inactivated in the germ line of animals using homologous recombination [Capecchi, Science 244:1288-1292 (1989)]. Animals in which the gene is over expressed, under the regulatory control of exogenous or endogenous promoter elements, are known as transgenic animals. Animals in which an endogenous gene has been inactivated by homologous recombination are referred to as “knockout” animals. Knockout animals, preferably non-human mammals, can be prepared as described in U.S. Pat. No. 5,557,032, incorporated herein by reference. Transgenic animals are useful to determine the roles polypeptides of the invention play in biological processes, and preferably in disease states. Transgenic animals are useful as model systems to identify compounds that modulate lipid metabolism. Transgenic animals, preferably non-human mammals, are produced using methods as described in U.S. Pat. No 5,489,743 and PCT Publication No. WO94/28122, incorporated herein by reference.

[0128] Transgenic animals can be prepared wherein all or part of a promoter of the polynucleotides of the invention is either activated or inactivated to alter the level of expression of the polypeptides of the invention. Inactivation can be carried out using homologous recombination methods described above. Activation can be achieved by supplementing or even replacing the homologous promoter to provide for increased protein expression. The homologous promoter can be supplemented by insertion of one or more heterologous enhancer elements known to confer promoter activation in a particular tissue.

[0129] The polynucleotides of the present invention also make possible the development, through, e.g., homologous recombination or knock out strategies, of animals that fail to express polypeptides of the invention or that express a variant polypeptide. Such animals are useful as models for studying the in vivo activities of polypeptide as well as for studying modulators of the polypeptides of the invention.

[0130] In preferred methods to determine biological functions of the polypeptides of the invention in vivo, one or more genes provided by the invention are either over expressed or inactivated in the germ line of animals using homologous recombination [Capecchi, Science 244:1288-1292 (1989)]. Animals in which the gene is over expressed, under the regulatory control of exogenous or endogenous promoter elements, are known as transgenic animals. Animals in which an endogenous gene has been inactivated by homologous recombination are referred to as “knockout” animals. Knockout animals, preferably non-human mammals, can be prepared as described in U.S. Pat. No. 5,557,032, incorporated herein by reference. Transgenic animals are useful to determine the roles polypeptides of the invention play in biological processes, and preferably in disease states. Transgenic animals are useful as model systems to identify compounds that modulate lipid metabolism. Transgenic animals, preferably non-human mammals, are produced using methods as described in U.S. Pat. No 5,489,743 and PCT Publication No. WO94/28122, incorporated herein by reference.

[0131] Transgenic animals can be prepared wherein all or part of the polynucleotides of the invention promoter is either activated or inactivated to alter the level of expression of the polypeptides of the invention. Inactivation can be carried out using homologous recombination methods described above. Activation can be achieved by supplementing or even replacing the homologous promoter to provide for increased protein expression. The homologous promoter can be supplemented by insertion of one or more heterologous enhancer elements known to confer promoter activation in a particular tissue.

USES AND BIOLOGICAL ACTIVITY

[0132] The polynucleotides and proteins of the present invention are expected to exhibit one or more of the uses or biological activities (including those associated with assays cited herein) identified herein. Uses or activities described for proteins of the present invention may be provided by administration or use of such proteins or of polynucleotides encoding such proteins (such as, for example, in gene therapies or vectors suitable for introduction of DNA). The mechanism underlying the particular condition or pathology will dictate whether the polypeptides of the invention, the polynucleotides of the invention or modulators (activators or inhibitors) thereof would be beneficial to the subject in need of treatment. Thus, “therapeutic compositions of the invention” include compositions comprising isolated polynucleotides (including recombinant DNA molecules, cloned genes and degenerate variants thereof) or polypeptides of the invention (including full length protein, mature protein and truncations or domains thereof), or compounds and other substances that modulate the overall activity of the target gene products, either at the level of target gene/protein expression or target protein activity. Such modulators include polypeptides, analogs, (variants), including fragments and fusion proteins, antibodies and other binding proteins; chemical compounds that directly or indirectly activate or inhibit the polypeptides of the invention (identified, e.g., via drug screening assays as described herein); antisense polynucleotides and polynucleotides suitable for triple helix formation; and in particular antibodies or other binding partners that specifically recognize one or more epitopes of the polypeptides of the invention.

[0133] The polypeptides of the present invention may likewise be involved in cellular activation or in one of the other physiological pathways described herein.

RESEARCH USES AND UTILITIES

[0134] The polynucleotides provided by the present invention can be used by the research community for various purposes. The polynucleotides can be used to express recombinant protein for analysis, characterization or therapeutic use; as markers for tissues in which the corresponding protein is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in disease states); as molecular weight markers on gels; as chromosome markers or tags (when labeled) to identify chromosomes or to map related gene positions; to compare with endogenous DNA sequences in patients to identify potential genetic disorders; as probes to hybridize and thus discover novel, related DNA sequences; as a source of information to derive PCR primers for genetic fingerprinting; as a probe to “subtract-out” known sequences in the process of discovering other novel polynucleotides; for selecting and making oligomers for attachment to a “gene chip” or other support, including for examination of expression patterns; to raise anti-protein antibodies using DNA immunization techniques; and as an antigen to raise anti-DNA antibodies or elicit another immune response. Where the polynucleotide encodes a protein which binds or potentially binds to another protein (such as, for example, in a receptor-ligand interaction), the polynucleotide can also be used in interaction trap assays (such as, for example, that described in Gyuris et al., Cell 75:791-803 (1993)) to identify polynucleotides encoding the other protein with which binding occurs or to identify inhibitors of the binding interaction.

[0135] The polypeptides provided by the present invention can similarly be used in assays to determine biological activity, including in a panel of multiple proteins for high-throughput screening; to raise antibodies or to elicit another immune response; as a reagent (including the labeled reagent) in assays designed to quantitatively determine levels of the protein (or its receptor) in biological fluids; as markers for tissues in which the corresponding polypeptide is preferentially expressed (either constitutively or at a particular stage of tissue differentiation or development or in a disease state); and, of course, to isolate correlative receptors or ligands. Proteins involved in these binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction.

[0136] Any or all of these research utilities are capable of being developed into reagent grade or kit format for commercialization as research products.

[0137] Methods for performing the uses listed above are well known to those skilled in the art. References disclosing such methods include without limitation “Molecular Cloning: A Laboratory Manual”, 2d ed., Cold Spring Harbor Laboratory Press, Sambrook, J., E. F. Fritsch and T. Maniatis eds., 1989, and “Methods in Enzymology: Guide to Molecular Cloning Techniques”, Academic Press, Berger, S. L. and A. R. Kimmel eds., 1987.

NUTRITIONAL USES

[0138] Polynucleotides and polypeptides of the present invention can also be used as nutritional sources or supplements. Such uses include without limitation use as a protein or amino acid supplement, use as a carbon source, use as a nitrogen source and use as a source of carbohydrate. In such cases the polypeptide or polynucleotide of the invention can be added to the feed of a particular organism or can be administered as a separate solid or liquid preparation, such as in the form of powder, pills, solutions, suspensions or capsules. In the case of microorganisms, the polypeptide or polynucleotide of the invention can be added to the medium in or on which the microorganism is cultured.

CYTOKINE AND CELL PROLIFERATION/DIFFERENTIATION ACTIVITY

[0139] A polypeptide of the present invention may exhibit activity relating to cytokine, cell proliferation (either inducing or inhibiting) or cell differentiation (either inducing or inhibiting) activity or may induce production of other cytokines in certain cell populations. A polynucleotide of the invention can encode a polypeptide exhibiting such attributes. Many protein factors discovered to date, including all known cytokines, have exhibited activity in one or more factor-dependent cell proliferation assays, and hence the assays serve as a convenient confirmation of cytokine activity. The activity of therapeutic compositions of the present invention is evidenced by any one of a number of routine factor dependent cell proliferation assays for cell lines including, without limitation, 32D, DA2, DA1G, T10, B9, B9/11, BaF3, MC9/G, M+(preB M+), 2E8, RB5, DA1, 123, T1165, HT2, CTLL2, TF-1, Mo7e, CMK, HLTVEC, and Caco. Therapeutic compositions of the invention can be used in the following:

[0140] Assays for T-cell or thymocyte proliferation include without limitation those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986; Bertagnolli et al., J. Immunol. 145:1706-1712, 1990; Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Bertagnolli, et al., I. Immunol. 149:3778-3783, 1992; Bowman et al., I. Immunol. 152:1756-1761, 1994.

[0141] Assays for cytokine production and/or proliferation of spleen cells, lymph node cells or thymocytes include, without limitation, those described in: Polyclonal T cell stimulation, Kruisbeek, A. M. and Shevach, E. M. In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 3.12.1-3.12.14, John Wiley and Sons, Toronto. 1994; and Measurement of mouse and human interleukin- , Schreiber, R. D. In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 6.8.1-6.8.8, John Wiley and Sons, Toronto. 1994.

[0142] Assays for proliferation and differentiation of hematopoietic and lymphopoietic cells include, without limitation, those described in: Measurement of Human and Murine Interleukin 2 and Interleukin 4, Bottomly, K., Davis, L. S. and Lipsky, P. E. In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 6.3.1-6.3.12, John Wiley and Sons, Toronto. 1991; deVries et al., J. Exp. Med. 173:1205-1211, 1991; Moreau et al., Nature 336:690-692, 1988; Greenberger et al., Proc. Natl. Acad. Sci. U.S.A. 80:2931-2938, 1983; Measurement of mouse and human interleukin 6—Nordan, R. In Current Protocols in Immunology. J. E. Coligan eds. Vol 1 pp. 6.6.1-6.6.5, John Wiley and Sons, Toronto. 1991; Smith et al., Proc. Natl. Aced. Sci. U.S.A. 83:1857-1861, 1986; Measurement of human Interleukin 11—Bennett, F., Giannotti, J., Clark, S. C. and Turner, K. J. In Current Protocols in hnuunology. J. E. Coligan eds. Vol 1 pp. 6.15.1 John Wiley and Sons, Toronto. 1991; Measurement of mouse and human Interleukin 9—Ciarletta, A., Giannotti, J., Clark, S. C. and Turner, K. J. In Current Protocols in Immunology. J. E. Coligan eds. Vol 1 pp. 6.13.1, John Wiley and Sons, Toronto. 1991.

[0143] Assays for T-cell clone responses to antigens (which will identify, among others, proteins that affect APC-T cell interactions as well as direct T-cell effects by measuring proliferation and cytokine production) include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, W Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function; Chapter 6, Cytokines and their cellular receptors; Chapter 7, Immunologic studies in Humans); Weinberger et al., Proc. Natl. Acad. Sci, USA 77:6091-6095, 1980; Weinberger et al., Eur. J. lmrun. 11:405-411, 1981; Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. hnnunol. 140:508-512, 1988.

STEM CELL GROWTH FACTOR ACTIVITY

[0144] A polypeptide of the present invention may exhibit stem cell growth factor activity and be involved in the proliferation, differentiation and survival of pluripotent and totipotent stem cells including primordial germ cells, embryonic stem cells, hematopoietic stem cells and/or germ line stem cells. Administration of the polypeptide of the invention to stem cells in vivo or ex vivo is expected to maintain and expand cell populations in a totipotential or pluripotential state which would be useful for re-engineering damaged or diseased tissues, transplantation, manufacture of biopharmaceuticals and the development of bio-sensors. The ability to produce large quantities of human cells has important working applications for the production of human proteins which currently must be obtained from non-human sources or donors, implantation of cells to treat diseases such as Parkinson's, Alzheimer's and other neurodegenerative diseases; tissues for grafting such as bone marrow, skin, cartilage, tendons, bone, muscle (including cardiac muscle), blood vessels, cornea, neural cells, gastrointestinal cells and others; and organs for transplantation such as kidney, liver, pancreas (including islet cells), heart and lung.

[0145] It is contemplated that multiple different exogenous growth factors and/or cytokines may be administered in combination with the polypeptide of the invention to achieve the desired effect, including any of the growth factors listed herein, other stem cell maintenance factors, and specifically including stem cell factor (SCF), leukemia inhibitory factor (LIF), Flt-3 ligand (Flt-3L), any of the interleukins, recombinant soluble IL-6 receptor fused to IL-6, macrophage inflammatory protein 1-alpha (MIP-1-alpha), G-CSF, GM-CSF, thrombopoietin (TPO), platelet factor 4 (PF-4), platelet-derived growth factor (PDGF), neural growth factors and basic fibroblast growth factor (bFGF).

[0146] Since totipotent stem cells can give rise to virtually any mature cell type, expansion of these cells in culture will facilitate the production of large quantities of mature cells. Techniques for culturing stem cells are known in the art and administration of polypeptides of the invention, optionally with other growth factors and/or cytokines, is expected to enhance the survival and proliferation of the stem cell populations. This can be accomplished by direct administration of the polypeptide of the invention to the culture medium. Alternatively, stroma cells transfected with a polynucleotide that encodes for the polypeptide of the invention can be used as a feeder layer for the stem cell populations in culture or in vivo. Stromal support cells for feeder layers may include embryonic bone marrow fibroblasts, bone marrow stromal cells, fetal liver cells, or cultured embryonic fibroblasts (see U.S. Pat. No. 5,690,926).

[0147] Stem cells themselves can be transfected with a polynucleotide of the invention to induce autocrine expression of the polypeptide of the invention. This will allow for generation of undifferentiated totipotential/pluripotential stem cell lines that are useful as is or that can then be differentiated into the desired mature cell types. These stable cell lines can also serve as a source of undifferentiated totipotential/pluripotential MRNA to create cDNA libraries and templates for polymerase chain reaction experiments. These studies would allow for the isolation and identification of differentially expressed genes in stem cell populations that regulate stem cell proliferation and/or maintenance.

[0148] Expansion and maintenance of totipotent stem cell populations will be useful in the treatment of many pathological conditions. For example, polypeptides of the present invention may be used to manipulate stem cells in culture to give rise to neuroepithelial cells that can be used to augment or replace cells damaged by illness, autoimmune disease, accidental damage or genetic disorders. The polypeptide of the invention may be useful for inducing the proliferation of neural cells and for the regeneration of nerve and brain tissue, i.e. for the treatment of central and peripheral nervous system diseases and neuropathies, as well as mechanical and traumatic disorders which involve degeneration, death or trauma to neural cells or nerve tissue. In addition, the expanded stem cell populations can also be genetically altered for gene therapy purposes and to decrease host rejection of replacement tissues after grafting or implantation.

[0149] Expression of the polypeptide of the invention and its effect on stem cells can also be manipulated to achieve controlled differentiation of the stem cells into more differentiated cell types. A broadly applicable method of obtaining pure populations of a specific differentiated cell type from undifferentiated stem cell populations involves the use of a cell-type specific promoter driving a selectable marker. The selectable marker allows only cells of the desired type to survive. For example, stem cells can be induced to differentiate into cardiomyocytes (Wobus et al., Differentiation, 48: 173-182, (1991); Klug et al., J. Clin. Invest., 98(1): 216-224, (1998)) or skeletal muscle cells (Browder, L. W. In: Principles of Tissue Engineering eds. Lanza et al., Academic Press (1997)). Alternatively, directed differentiation of stem cells can be accomplished by culturing the stem cells in the presence of a differentiation factor such as retinoic acid and an antagonist of the polypeptide of the invention which would inhibit the effects of endogenous stem cell factor activity and allow differentiation to proceed.

[0150] In vitro cultures of stem cells can be used to determine if the polypeptide of the invention exhibits stem cell growth factor activity. Stem cells are isolated from any one of various cell sources (including hematopoietic stem cells and embryonic stem cells) and cultured on a feeder layer, as described by Thompson et al. Proc. Natl. Acad. Sci, U.S.A., 92: 7844-7848 (1995), in the presence of the polypeptide of the invention alone or in combination with other growth factors or cytokines. The ability of the polypeptide of the invention to induce stem cells proliferation is determined by colony formation on semisolid support e.g. as described by Bernstein et al., Blood, 77: 2316-2321 (1991).

HEMATOPOIESIS REGULATING ACTIVITY

[0151] A polypeptide of the present invention may be involved in regulation of hematopoiesis and, consequently, in the treatment of myeloid or lymphoid cell disorders. Even marginal biological activity in support of colony forming cells or of factor-dependent cell lines indicates involvement in regulating hematopoiesis, e.g. in supporting the growth and proliferation of erythroid progenitor cells alone or in combination with other cytokines, thereby indicating utility, for example, in treating various anemias or for use in conjunction with irradiation/chemotherapy to stimulate the production of erythroid precursors and/or erythroid cells; in supporting the growth and proliferation of myeloid cells such as granulocytes and monocytes/macrophages (i.e., traditional CSF activity) useful, for example, in conjunction with chemotherapy to prevent or treat consequent myelo-suppression; in supporting the growth and proliferation of megakaryocytes and consequently of platelets thereby allowing prevention or treatment of various platelet disorders such as thrombocytopenia, and generally for use in place of or complimentary to platelet transfusions; and/or in supporting the growth and proliferation of hematopoietic stem cells which are capable of maturing to any and all of the above-mentioned hematopoietic cells and therefore find therapeutic utility in various stem cell disorders (such as those usually treated with transplantation, including, without limitation, aplastic anemia and paroxysmal nocturnal hemoglobinuria), as well as in repopulating the stem cell compartment post irradiation/chemotherapy, either in-vivo or ex-vivo (i.e., in conjunction with bone marrow transplantation or with peripheral progenitor cell transplantation (homologous or heterologous)) as normal cells or genetically manipulated for gene therapy.

[0152] Therapeutic compositions of the invention can be used in the following:

[0153] Suitable assays for proliferation and differentiation of various hematopoietic lines are cited above.

[0154] Assays for embryonic stem cell differentiation (which will identify, among others, proteins that influence embryonic differentiation hematopoiesis) include, without limitation, those described in: Johansson et al. Cellular Biology 15:141-151, 1995; Keller et al., Molecular and Cellular Biology 13:473-486, 1993; McClanahan et al., Blood 81:2903-2915, 1993.

[0155] Assays for stem cell survival and differentiation (which will identify, among others, proteins that regulate lympho-hematopoiesis) include, without limitation, those described in: Methylcellulose colony fonning assays, Freshney, M. G. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 265-268, Wiley-Liss, Inc., New York, N.Y. 1994; Hirayama et al., Proc. Natl. Acad. Sci. USA 89:5907-5911, 1992; Primitive hematopoietic colony forming cells with high proliferative potential, McNiece, I. K. and Briddell, R. A. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 23-39, Wiley-Liss, Inc., New York, N.Y. 1994; Neben et al., Experimental Hematology 22:353-359, 1994; Cobblestone area forming cell assay, Ploemacher, R. E. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 1-21, Wiley-Liss, Inc., New York, N.Y. 1994; Long term bone marrow cultures in the presence of stromal cells, Spooncer, E., Dexter, M. and Allen, T. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 163-179, Wiley-Liss, Inc., New York, N.Y. 1994; Long term culture initiating cell assay, Sutherland, H. J. In Culture of Hematopoietic Cells. R. I. Freshney, et al. eds. Vol pp. 139-162, Wiley-Liss, Inc., New York, N.Y. 1994.

TISSUE GROWTH ACTIVITY

[0156] A polypeptide of the present invention also may be involved in bone, cartilage, tendon, ligament and/or nerve tissue growth or regeneration, as well as in wound healing and tissue repair and replacement, and in healing of burns, incisions and ulcers.

[0157] A polypeptide of the present invention which induces cartilage and/or bone growth in circumstances where bone is not normally formed, has application in the healing of bone fractures and cartilage damage or defects in humans and other animals. Compositions of a polypeptide, antibody, binding partner, or other modulator of the invention may have prophylactic use in closed as well as open fracture reduction and also in the improved fixation of artificial joints. De novo bone formation induced by an osteogenic agent contributes to the repair of congenital, trauma induced, or oncologic resection induced craniofacial defects, and also is useful in cosmetic plastic surgery.

[0158] A polypeptide of this invention may also be involved in attracting bone-forming cells, stimulating growth of bone-forming cells, or inducing differentiation of progenitors of bone-forming cells. Treatment of osteoporosis, osteoarthritis, bone degenerative disorders, or periodontal disease, such as through stimulation of bone and/or cartilage repair or by blocking inflammation or processes of tissue destruction (collagenase activity, osteoclast activity, etc.) mediated by inflammatory processes may also be possible using the composition of the invention.

[0159] Another category of tissue regeneration activity that may involve the polypeptide of the present invention is tendon/ligamnent formation. Induction of tendon/ligament-like tissue or other tissue formation in circumstances where such tissue is not normally formed, has application in the healing of tendon or ligament tears, deformities and other tendon or ligament defects in humans and other animals. Such a preparation employing a tendon/ligament-like tissue inducing protein may have prophylactic use in preventing damage to tendon or ligament tissue, as well as use in the improved fixation of tendon or ligament to bone or other tissues, and in repairing defects to tendon or ligament tissue. De novo tendon/ligament-like tissue formation induced by a composition of the present invention contributes to the repair of congenital, trauma induced, or other tendon or ligament defects of other origin, and is also useful in cosmetic plastic surgery for attachment or repair of tendons or ligaments. The compositions of the present invention may provide environment to attract tendon- or ligament-forming cells, stimulate growth of tendon- or ligament-forming cells, induce differentiation of progenitors of tendon- or ligament-forming cells, or induce growth of tendon/ligament cells or progenitors ex vivo for return in vivo to effect tissue repair. The compositions of the invention may also be useful in the treatment of tendinitis, carpal tunnel syndrome and other tendon or ligament defects. The compositions may also include an appropriate matrix and/or sequestering agent as a carrier as is well known in the art.

[0160] The compositions of the present invention may also be useful for proliferation of neural cells and for regeneration of nerve and brain tissue, i.e. for the treatment of central and peripheral nervous system diseases and neuropathies, as well as mechanical and traumatic disorders, which involve degeneration, death or trauma to neural cells or nerve tissue. More specifically, a composition may be used in the treatment of diseases of the peripheral nervous system, such as peripheral nerve injuries, peripheral neuropathy and localized neuropathies, and central nervous system diseases, such as Alzheimer's, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and Shy-Drager syndrome. Further conditions which may be treated in accordance with the present invention include mechanical and traumatic disorders, such as spinal cord disorders, head trauma and cerebrovascular diseases such as stroke. Peripheral neuropathies resulting from chemotherapy or other medical therapies may also be treatable using a composition of the invention.

[0161] Compositions of the invention may also be useful to promote better or faster closure of non-healing wounds, including without limitation pressure ulcers, ulcers associated with vascular insufficiency, surgical and traumatic wounds, and the like.

[0162] Compositions of the present invention may also be involved in the generation or regeneration of other tissues, such as organs (including, for example, pancreas, liver, intestine, kidney, skin, endothelium), muscle (smooth, skeletal or cardiac) and vascular (including vascular endothelium) tissue, or for promoting the growth of cells comprising such tissues. Part of the desired effects may be by inhibition or modulation of fibrotic scarring may allow normal tissue to regenerate. A polypeptide of the present invention may also exhibit angiogenic activity.

[0163] A composition of the present invention may also be useful for gut protection or regeneration and treatment of lung or liver fibrosis, reperfusion injury in various tissues, and conditions resulting from systemic cytokine damage.

[0164] A composition of the present invention may also be useful for promoting or inhibiting differentiation of tissues described above from precursor tissues or cells; or for inhibiting the growth of tissues described above.

[0165] Therapeutic compositions of the invention can be used in the following:

[0166] Assays for tissue generation activity include, without limitation, those described in: International Patent Publication No. WO95/16035 (bone, cartilage, tendon); International Patent Publication No. WO95/05846 (nerve, neuronal); International Patent Publication No. WO91/07491 (skin, endothelium).

[0167] Assays for wound healing activity include, without limitation, those described in: Winter, Epidermal Wound Healing, pps. 71-112 (Maibach, H. 1. and Rovee, D. T., eds.), Year Book Medical Publishers, Inc., Chicago, as modified by Eaglstein and Mertz, J. Invest. Dermatol 71:382-84 (1978).

IMMUNE STIMULATING OR SUPPRESSING ACTIVITY

[0168] A polypeptide of the present invention may also exhibit immune stimulating or immune suppressing activity, including without limitation the activities for which assays are described herein. A polynucleotide of the invention can encode a polypeptide exhibiting such activities. A protein may be useful in the treatment of various immune deficiencies and disorders (including severe combined immunodeficiency (SCID)), e.g., in regulating (up or down) growth and proliferation of T and/or B lymphocytes, as well as effecting the cytolytic activity of NK cells and other cell populations. These immune deficiencies may be genetic or be caused by viral (e.g., HIV) as well as bacterial or fungal infections, or may result from autoimmune disorders. More specifically, infectious diseases causes by viral, bacterial, fungal or other infection may be treatable using a protein of the present invention, including infections by HIV, hepatitis viruses, herpes viruses, mycobacteria, Leishmania spp., malaria spp. and various fungal infections such as candidiasis. Of course, in this regard, proteins of the present invention may also be useful where a boost to the immune system generally may be desirable, i.e., in the treatment of cancer.

[0169] Autoimmune disorders which may be treated using a protein of the present invention include, for example, connective tissue disease, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, autoimmune pulmonary inflammation, Guillain-Barre syndrome, autoimmune thyroiditis, insulin dependent diabetes mellitis, myasthenia gravis, graft-versus-host disease and autoirnmune inflammatory eye disease. Such a protein (or antagonists thereof, including antibodies) of the present invention may also to be useful in the treatment of allergic reactions and conditions (e.g., anaphylaxis, serum sickness, drug reactions, food allergies, insect venom allergies, mastocytosis, allergic rhinitis, hypersensitivity pneumonitis, urticaria, angioedema, eczema, atopic dermatitis, allergic contact dermatitis, erythema multiforme, Stevens-Johnson syndrome, allergic conjunctivitis, atopic keratoconjunctivitis, venereal keratoconjunctivitis, giant papillary conjunctivitis and contact allergies), such as asthma (particularly allergic asthma) or other respiratory problems. Other conditions, in which immune suppression is desired (including, for example, organ transplantation), may also be treatable using a protein (or antagonists thereof) of the present invention. The therapeutic effects of the polypeptides or antagonists thereof on allergic reactions can be evaluated by in vivo animals models such as the cumulative contact enhancement test (Lastbom et al., Toxicology 125: 59-66, 1998), skin prick test (Hoffmann et al., Allergy 54: 446-54, 1999), guinea pig skin sensitization test (Vohr et al., Arch. Toxocol. 73: 501-9), and murine local lymph node assay (Kimber et al., J. Toxicol. Environ. Health 53: 563-79).

[0170] Using the proteins of the invention it may also be possible to modulate immune responses, in a number of ways. Down regulation may be in the form of inhibiting or blocking an immune response already in progress or may involve preventing the induction of an immune response. The functions of activated T cells may be inhibited by suppressing T cell responses or by inducing specific tolerance in T cells, or both. Imnmunosuppression of T cell responses is generally an active, non-antigen-specific, process which requires continuous exposure of the T cells to the suppressive agent. Tolerance, which involves inducing non-responsiveness or anergy in T cells, is distinguishable from immunosuppression in that it is generally antigen-specific and persists after exposure to the tolerizing agent has ceased. Operationally, tolerance can be demonstrated by the lack of a T cell response upon reexposure to specific antigen in the absence of the tolerizing agent.

[0171] Down regulating or preventing one or more antigen functions (including without limitation B lymphocyte antigen functions (such as, for example, B7)), e.g., preventing high level lymphokine synthesis by activated T cells, will be useful in situations of tissue, skin and organ transplantation and in graft-versus-host disease (GVHD). For example, blockage of T cell function should result in reduced tissue destruction in tissue transplantation. Typically, in tissue transplants, rejection of the transplant is initiated through its recognition as foreign by T cells, followed by an immune reaction that destroys the transplant. The administration of a therapeutic composition of the invention may prevent cytokine synthesis by immune cells, such as T cells, and thus acts as an immunosuppressant. Moreover, a lack of costimulation may also be sufficient to anergize the T cells, thereby inducing tolerance in a subject. Induction of long-term tolerance by B lymphocyte antigen-blocking reagents may avoid the necessity of repeated administration of these blocking reagents. To achieve sufficient immunosuppression or tolerance in a subject, it may also be necessary to block the function of a combination of B lymphocyte antigens.

[0172] The efficacy of particular therapeutic compositions in preventing organ transplant rejection or GVHD can be assessed using animal models that are predictive of efficacy in humans. Examples of appropriate systems which can be used include allogeneic cardiac grafts in rats and xenogeneic pancreatic islet cell grafts in mice, both of which have been used to examine the immunosuppressive effects of CTLA4Ig fusion proteins in vivo as described in Lenschow et al., Science 257:789-792 (1992) and Turka et al., Proc. Natl. Acad. Sci USA, 89:11102-11105 (1992). In addition, murine models of GVHD (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 846-847) can be used to determine the effect of therapeutic compositions of the invention on the development of that disease.

[0173] Blocking antigen function may also be therapeutically useful for treating autoimmune diseases. Many autoimmune disorders are the result of inappropriate activation of T cells that are reactive against self tissue and which promote the production of cytokines and autoantibodies involved in the pathology of the diseases. Preventing the activation of autoreactive T cells may reduce or eliminate disease symptoms. Administration of reagents which block stimulation of T cells can be used to inhibit T cell activation and prevent production of autoantibodies or T cell-derived cytolidnes which may be involved in the disease process. Additionally, blocking reagents may induce antigen-specific tolerance of autoreactive T cells which could lead to long-term relief from the disease. The efficacy of blocking reagents in preventing or alleviating autoimmune disorders can be determined using a number of well-characterized animal models of human autoimmune diseases. Examples include murine experimental autoimmune encephalitis, systemic lupus erythmatosis in MRL/lpr/lpr mice or NZB hybrid mice, murine autoimmune collagen arthritis, diabetes mellitus in NOD mice and BB rats, and murine experimental myasthenia gravis (see Paul ed., Fundamental Immunology, Raven Press, New York, 1989, pp. 840-856).

[0174] Upregulation of an antigen function (e.g., a B lymphocyte antigen function), as a means of up regulating immune responses, may also be useful in therapy. Upregulation of immune responses may be in the foim of enhancing an existing immune response or eliciting an initial immune response. For example, enhancing an immune response may be useful in cases of viral infection, including systemic viral diseases such as influenza, the common cold, and encephalitis.

[0175] Alternatively, anti-viral immune responses may be enhanced in an infected patient by removing T cells from the patient, costimulating the T cells in vitro with viral antigen-pulsed APCs either expressing a peptide of the present invention or together with a stimulatory form of a soluble peptide of the present invention and reintroducing the in vitro activated T cells into the patient. Another method of enhancing anti-viral immune responses would be to isolate infected cells from a patient, transfect them with a nucleic acid encoding a protein of the present invention as described herein such that the cells express all or a portion of the protein on their surface, and reintroduce the transfected cells into the patient. The infected cells would now be capable of delivering a costimulatory signal to, and thereby activate, T cells in vivo.

[0176] A polypeptide of the present invention may provide the necessary stimulation signal to T cells to induce a T cell mediated immune response against the transfected tumor cells. In addition, tumor cells which lack MHC class I or MHC class II molecules, or which fail to reexpress sufficient mounts of MHC class I or MHC class II molecules, can be transfected with nucleic acid encoding all or a portion of (e.g., a cytoplasmic-domain truncated portion) of an MHC class I alpha chain protein and β₂ microglobulin protein or an MUC class II alpha chain protein and an MHC class II beta chain protein to thereby express MHC class I or MHC class II proteins on the cell surface. Expression of the appropriate class I or class II MHC in conjunction with a peptide having the activity of a B lymphocyte antigen (e.g., B7-1, B7-2, B7-3) induces a T cell mediated immune response against the transfected tumor cell. Optionally, a gene encoding an antisense construct which blocks expression of an MHC class II associated protein, such as the invariant chain, can also be cotransfected with a DNA encoding a peptide having the activity of a B lymphocyte antigen to promote presentation of tumor associated antigens and induce tumor specific immunity. Thus, the induction of a T cell mediated immune response in a human subject may be sufficient to overcome tumor-specific tolerance in the subject.

[0177] The activity of a protein of the invention may, among other means, be measured by the following methods:

[0178] Suitable assays for thymocyte or splenocyte cytotoxicity include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A. M. Krtiisbeek, D. H. Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Herrmann et al., Proc. Natl. Acad. Sci. USA 78:2488-2492, 1981; Herrmann et al., J. Immunol. 128:1968-1974, 1982; Handa et al., J. Immunol. 135:1564-1572, 1985; Takai et al., I. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988; Bowman et al., J. Virology 61:1992-1998; Bertagnolli et al., Cellular Immunology 133:327-341, 1991; Brown et al., J. Immunol. 153:3079-3092, 1994.

[0179] Assays for T-cell-dependent immunoglobulin responses and isotype switching (which will identify, among others, proteins that modulate T-cell dependent antibody responses and that affect Th1/Th2 profiles) include, without limitation, those described in: Maliszewski, J. Immunol. 144:3028-3033, 1990; and Assays for B cell function: In vitro antibody production, Mond, J. J. and Brunswick, M. In Current Protocols in Immunology. J. E. e.a. Coligan eds. Vol 1 pp. 3.8.1-3.8.16, John Wiley and Sons, Toronto. 1994.

[0180] Mixed lymphocyte reaction (MLR) assays (which will identify, among others, proteins that generate predominantly Th1 and CTL responses) include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 3, In Vitro assays for Mouse Lymphocyte Function 3.1-3.19; Chapter 7, Immunologic studies in Humans); Takai et al., J. Immunol. 137:3494-3500, 1986; Takai et al., J. Immunol. 140:508-512, 1988; Bertagnolli et al., J. Immunol. 149:3778-3783, 1992.

[0181] Dendritic cell-dependent assays (which will identify, among others, proteins expressed by dendritic cells that activate naive T-cells) include, without limitation, those described in: Guery et al., J. Immunol. 134:536-544, 1995; Inaba et al., Journal of Experimental Medicine 173:549-559, 1991; Macatonia et al., Journal of Immunology 154:5071-5079, 1995; Porgador et al., Journal of Experimental Medicine 182:255-260, 1995; Nair et al., Journal of Virology 67:4062-4069, 1993; Huang et al., Science 264:961-965, 1994; Macatonia et al., Journal of Experimental Medicine 169:1255-1264, 1989; Bhardwaj et al., Journal of Clinical Investigation 94:797-807, 1994; and Inaba et al., Journal of Experimental Medicine 172:631-640, 1990.

[0182] Assays for lymphocyte survival/apoptosis (which will identify, among others, proteins that prevent apoptosis after superantigen induction and proteins that regulate lymphocyte homeostasis) include, without limitation, those described in: Darzynkiewicz et al., Cytometry 13:795-808, 1992; Gorczyca et al., Leukemia 7:659-670, 1993; Gorczyca et al., Cancer Research 53:1945-1951, 1993; Itoh et al., Cell 66:233-243, 1991; Zacharchuk, Journal of Immunology 145:4037-4045, 1990; Zamai et al., Cytometry 14:891-897, 1993; Gorczyca et al., International Journal of Oncology 1:639-648, 1992.

[0183] Assays for proteins that influence early steps of T-cell commitment and development include, without limitation, those described in: Antica et al., Blood 84:111-117, 1994; Fine et al., Cellular Immunology 155:111-122, 1994; Galy et al., Blood 85:2770-2778, 1995; Toki et al., Proc. Nat. Acad Sci. USA 88:7548-7551, 1991.

ACTIVIN/INHIBIN ACTIVITY

[0184] A polypeptide of the present invention may also exhibit activin- or inhibin-related activities. A polynucleotide of the invention may encode a polypeptide exhibiting such characteristics. Inhibins are characterized by their ability to inhibit the release of follicle stimulating hormone (FSH), while activins and are characterized by their ability to stimulate the release of follicle stimulating hormone (FSH). Thus, a polypeptide of the present invention, alone or in heterodimers with a member of the inhibin family, may be useful as a contraceptive based on the ability of inhibins to decrease fertility in female mammals and decrease spermatogenesis in male mammals. Administration of sufficient amounts of other inhibins can induce infertility in these mammals. Alternatively, the polypeptide of the invention, as a homodimer or as a heterodimer with other protein subunits of the inhibin group, may be useful as a fertility inducing therapeutic, based upon the ability of activin molecules in stimulating FSH release from cells of the anterior pituitary. See, for example, U.S. Pat. No. 4,798,885. A polypeptide of the invention may also be useful for advancement of the onset of fertility in sexually immature mammals, so as to increase the lifetime reproductive performance of domestic animals such as, but not limited to, cows, sheep and pigs.

[0185] The activity of a polypeptide of the invention may, among other means, be measured by the following methods.

[0186] Assays for activin/inhibin activity include, without limitation, those described in: Vale et al., Endocrinology 91:562-572, 1972; Ling et al., Nature 321:779-782, 1986; Vale et al., Nature 321:776-779, 1986; Mason et al., Nature 318:659-663, 1985; Forage et al., Proc. Natl. Acad. Sci. USA 83:3091-3095, 1986.

CHEMOTACTIC/CHEMOKINETIC ACTIVITY

[0187] A polypeptide of the present invention may be involved in chemotactic or chemokinetic activity for mammalian cells, including, for example, monocytes, fibroblasts, neutrophils, T-cells, mast cells, eosinophils, epithelial and/or endothelial cells. A polynucleotide of the invention can encode a polypeptide exhibiting such attributes. Chemotactic and chemokinetic receptor activation can be used to mobilize or attract a desired cell population to a desired site of action. Chemotactic or chemokinetic compositions (e.g. proteins, antibodies, binding partners, or modulators of the invention) provide particular advantages in treatment of wounds and other trauma to tissues, as well as in treatment of localized infections. For example, attraction of lymphocytes, monocytes or neutrophils to tumors or sites of infection may result in improved immune responses against the tumor or infecting agent.

[0188] A protein or peptide has chemotactic activity for a particular cell population if it can stimulate, directly or indirectly, the directed orientation or movement of such cell population. Preferably, the protein or peptide has the ability to directly stimulate directed movement of cells. Whether a particular protein has chemotactic activity for a population of cells can be readily determined by employing such protein or peptide in any known assay for cell chemotaxis.

[0189] Therapeutic compositions of the invention can be used in the following:

[0190] Assays for chemotactic activity (which will identify proteins that induce or prevent chemotaxis) consist of assays that measure the ability of a protein to induce the migration of cells across a membrane as well as the ability of a protein to induce the adhesion of one cell population to another cell population. Suitable assays for movement and adhesion include, without limitation, those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Marguiles, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley-Interscience (Chapter 6.12, Measurement of alpha and beta Chemokines 6.12.1-6.12.28; Taub et al. J. Clin. Invest. 95:1370-1376, 1995; Lind et al. APMIS 103:140-146, 1995; Muller et al Eur. J. Immunol. 25:1744-1748; Gruber et al. J. of Immunol. 152:5860-5867, 1994; Johnston et al. J. of Immunol. 153:1762-1768, 1994.

HEMOSTATIC AND THROMBOLYTIC ACTIVITY

[0191] A polypeptide of the invention may also be involved in hemostatis or thrombolysis or thrombosis. A polynucleotide of the invention can encode a polypeptide exhibiting such attributes. Compositions may be useful in treatment of various coagulation disorders (including hereditary disorders, such as hemophilias) or to enhance coagulation and other hemostatic events in treating wounds resulting from trauma, surgery or other causes. A composition of the invention may also be useful for dissolving or inhibiting formation of thromboses and for treatment and prevention of conditions resulting therefrom (such as, for example, infarction of cardiac and central nervous system vessels (e.g., stroke).

[0192] Therapeutic compositions of the invention can be used in the following:

[0193] Assay for hemostatic and thrombolytic activity include, without limitation, those described in: Linet et al., J. Clin. Pharmacol. 26:131-140, 1986; Burdick et al., Thrombosis Res. 45:413-419, 1987; Humphrey et al., Fibrinolysis 5:71-79 (1991); Schaub, Prostaglandins 35:467-474, 1988.

CANCER DIAGNOSIS AND THERAPY

[0194] Polypeptides of the invention may be involved in cancer cell generation, proliferation or metastasis. Detection of the presence or amount of polynucleotides or polypeptides of the invention may be useful for the diagnosis and/or prognosis of one or more types of cancer. For example, the presence or increased expression of a polynucleotide/polypeptide of the invention may indicate a hereditary risk of cancer, a precancerous condition, or an ongoing malignancy. Conversely, a defect in the gene or absence of the polypeptide may be associated with a cancer condition. Identification of single nucleotide polymorphisms associated with cancer or a predisposition to cancer may also be useful for diagnosis or prognosis.

[0195] Cancer treatments promote tumor regression by inhibiting tumor cell proliferation, inhibiting angiogenesis (growth of new blood vessels that is necessary to support tumor growth) and/or prohibiting metastasis by reducing tumor cell motility or invasiveness. Therapeutic compositions of the invention may be effective in adult and pediatric oncology including in solid phase tumors/malignancies, locally advanced tumors, human soft tissue sarcomas, metastatic cancer, including lymphatic metastases, blood cell malignancies including multiple myeloma, acute and chronic leukemias, and lymphomas, head and neck cancers including mouth cancer, larynx cancer and thyroid cancer, lung cancers including small cell carcinoma and non-small cell cancers, breast cancers including small cell carcinoma and ductal carcinoma, gastrointestinal cancers including esophageal cancer, stomach cancer, colon cancer, colorectal cancer and polyps associated with colorectal neoplasia, pancreatic cancers, liver cancer, urologic cancers including bladder cancer and prostate cancer, malignancies of the female genital tract including ovarian carcinoma, uterine (including endometrial) cancers, and solid tumor in the ovarian follicle, kidney cancers including renal cell carcinoma, brain cancers including intrinsic brain tumors, neuroblastoma, astrocytic brain tumors, gliomas, metastatic tumor cell invasion in the central nervous system, bone cancers including osteomas, skin cancers including malignant melanoma, tumor progression of human skin keratinocytes, squamous cell carcinoma, basal cell carcinoma, hemangiopericytoma and Karposi's sarcoma.

[0196] Polypeptides, polynucleotides, or modulators of polypeptides of the invention (including inhibitors and stimulators of the biological activity of the polypeptide of the invention) may be administered to treat cancer. Therapeutic compositions can be administered in therapeutically effective dosages alone or in combination with adjuvant cancer therapy such as surgery, chemotherapy, radiotherapy, thennotherapy, and laser therapy, and may provide a beneficial effect, e.g. reducing tumor size, slowing rate of tumor growth, inhibiting metastasis, or otherwise improving overall clinical condition, without necessarily eradicating the cancer.

[0197] The composition can also be administered in therapeutically effective amounts as a portion of an anti-cancer cocktail. An anti-cancer cocktail is a mixture of the polypeptide or modulator of the invention with one or more anti-cancer drugs in addition to a pharmaceutically acceptable carrier for delivery. The use of anti-cancer cocktails as a cancer treatment is routine. Anti-cancer drugs that are well known in the art and can be used as a treatment in combination with the polypeptide or modulator of the invention include: Actinomycin D, Aninoglutethimide, Asparaginase, Bleomycin, Busulfan, Carboplatin, Carmustine, Chlorambucil, Cisplatin (cis-DDP), Cyclophosphamide, Cytarabine HCl (Cytosine arabinoside), Dacarbazine, Dactinomycin, Daunorubicin HCl, Doxorubicin HCl, Estramustine phosphate sodium, Etoposide (V16-213), Floxuridine, 5-Fluorouracil (5-Fu), Flutamide, Hydroxyurea (hydroxycarbamide), Ifosfamide, Interferon Alpha-2a, Interferon Alpha-2b, Leuprolide acetate (LHRH-releasing factor analog), Lomustine, Mechlorethamine HCl (nitrogen mustard), Melphalan, Mercaptopurine, Mesna, Methotrexate (MTX), Mitomycin, Mitoxantrone HCl, Octreotide, Plicamycin, Procarbazine HCl, Streptozocin, Tamoxifen citrate, Thioguanine, Thiotepa, Vinblastine sulfate, Vincristine sulfate, Amsacrine, Azacitidine, Hexamethylmelamine, Interleukin-2, Mitoguazone, Pentostatin, Semustine, Teniposide, and Vindesine sulfate.

[0198] In addition, therapeutic compositions of the invention may be used for prophylactic treatment of cancer. There are hereditary conditions and/or environmental situations (e.g. exposure to carcinogens) known in the art that predispose an individual to developing cancers. Under these circumstances, it may be beneficial to treat these individuals with therapeutically effective doses of the polypeptide of the invention to reduce the risk of developing cancers.

[0199] In vitro models can be used to determine the effective doses of the polypeptide of the invention as a potential cancer treatment. These in vitro models include proliferation assays of cultured tumor cells, growth of cultured tumor cells in soft agar (see Freshney, (1987) Culture of Animal Cells: A Manual of Basic Technique, Wily-Liss, New York, N.Y. Ch 18 and Ch 21), tumor systems in nude mice as described in Giovanella et al., J. Natl. Can. Inst., 52: 921-30 (1974), mobility and invasive potential of tumor cells in Boyden Chamber assays as described in Pilkington et al., Anticancer Res., 17: 4107-9 (1997), and angiogenesis assays such as induction of vascularization of the chick chorioallantoic membrane or induction of vascular endothelial cell migration as described in Ribatta et al., Intl. J. Dev. Biol., 40: 1189-97 (1999) and Li et al., Clin. Exp. Metastasis, 17:423-9 (1999), respectively. Suitable tumor cells lines are available, e.g. from American Type Tissue Culture Collection catalogs.

RECEPTOR/LIGAND ACTIVITY

[0200] A polypeptide of the present invention may also demonstrate activity as receptor, receptor ligand or inhibitor or agonist of receptor/ligand interactions. A polynucleotide of the invention can encode a polypeptide exhibiting such characteristics. Examples of such receptors and ligands include, without limitation, cytokine receptors and their ligands, receptor kinases and their ligands, receptor phosphatases and their ligands, receptors involved in cell-cell interactions and their ligands (including without limitation, cellular adhesion molecules (such as selecting, integrins and their ligands) and receptor/ligand pairs involved in antigen presentation, antigen recognition and development of cellular and humoral immune responses. Receptors and ligands are also useful for screening of potential peptide or small molecule inhibitors of the relevant receptor/ligand interaction. A protein of the present invention (including, without limitation, fragments of receptors and ligands) may themselves be useful as inhibitors of receptor/ligand interactions.

[0201] The activity of a polypeptide of the invention may, among other means, be measured by the following methods:

[0202] Suitable assays for receptor-ligand activity include without limitation those described in: Current Protocols in Immunology, Ed by J. E. Coligan, A. M. Kruisbeek, D. H. Margulies, E. M. Shevach, W. Strober, Pub. Greene Publishing Associates and Wiley- Interscience (Chapter 7.28, Measurement of Cellular Adhesion under static conditions 7.28.1-7.28.22), Takai et al., Proc. Natl. Acad. Sci. USA 84:6864-6868, 1987; Bierer et al., J. Exp. Med. 168:1145-1156, 1988; Rosenstein et al., J. Exp. Med. 169:149-160 1989; Stoltenborg et al., J. Immunol. Methods 175:59-68, 1994; Stitt et al., Cell 80:661-670, 1995.

[0203] By way of example, the polypeptides of the invention may be used as a receptor for a ligand(s) thereby transmitting the biological activity of that ligand(s). Ligands may be identified through binding assays, affinity chromatography, dihybrid screening assays, BIAcore assays, gel overlay assays, or other methods known in the art.

[0204] Studies characterizing drugs or proteins as agonist or antagonist or partial agonists or a partial antagonist require the use of other proteins as competing ligands. The polypeptides of the present invention or ligand(s) thereof may be labeled by being coupled to radioisotopes, calorimetric molecules or a toxin molecules by conventional methods. (“Guide to Protein Purification” Murray P. Deutscher (ed) Methods in Enzymology Vol. 182 (1990) Academic Press, Inc. San Diego). Examples of radioisotopes include, but are not limited to, tritium and carbon-14 . Examples of calorimetric molecules include, but are not limited to, fluorescent molecules such as fluorescamine, or rhodarnine or other colorimetric molecules. Examples of toxins include, but are not limited, to ricin.

DRUG SCREENING

[0205] This invention is particularly useful for screening chemical compounds by using the novel polypeptides or binding fragments thereof in any of a variety of drug screening techniques. The polypeptides or fragments employed in such a test may either be free in solution, affixed to a solid support, borne on a cell surface or located intracellularly. One method of drug screening utilizes eukaryotic or prokaryotic host cells which are stably transformed with recombinant nucleic acids expressing the polypeptide or a fragment thereof. Drugs are screened against such transformed cells in competitive binding assays. Such cells, either in viable or fixed form, can be used for standard binding assays. One may measure, for example, the formation of complexes between polypeptides of the invention or fragments and the agent being tested or examine the diminution in complex formation between the novel polypeptides and an appropriate cell line, which are well known in the art.

[0206] Sources for test compounds that may be screened for ability to bind to or modulate (i.e., increase or decrease) the activity of polypeptides of the invention include (1) inorganic and organic chemical libraries, (2) natural product libraries, and (3) combinatorial libraries comprised of either random or mimetic peptides, oligonucleotides or organic molecules.

[0207] Chemical libraries may be readily synthesized or purchased from a number of commercial sources, and may include structural analogs of known compounds or compounds that are identified as “hits” or “leads” via natural product screening.

[0208] The sources of natural product libraries are microorganisms (including bacteria and fungi), animals, plants or other vegetation, or marine organisms, and libraries of mixtures for screening may be created by: (1) fermentation and extraction of broths from soil, plant or marine microorganisms or (2) extraction of the organisms themselves. Natural product libraries include polyketides, non-ribosomal peptides, and (non-naturally occurring) variants thereof. For a review, see Science 282:63-68 (1998).

[0209] Combinatorial libraries are composed of large numbers of peptides, oligonucleotides or organic compounds and can be readily prepared by traditional automated synthesis methods, PCR, cloning or proprietary synthetic methods. Of particular interest are peptide and oligonucleotide combinatorial libraries. Still other libraries of interest include peptide, protein, peptidomimetic, multiparallel synthetic collection, recombinatorial, and polypeptide libraries. For a review of combinatorial chemistry and libraries created therefrom, see Myers, Curr. Opin. Biotechnol. 8:701-707 (1997). For reviews and examples of peptidomimetic libraries, see Al-Obeidi et al., Mol Biotechnol, 9(3):205-23 (1998); Hruby et al., Curr Opin Chem Biol, 1(1):114-19 (1997); Dorner et al., Bioorg Med Chem, 4(5):709-15 (1996) (alkylated dipeptides).

[0210] Identification of modulators through use of the various libraries described herein permits modification of the candidate “hit” (or “lead”) to optimize the capacity of the “hit” to bind a polypeptide of the invention. The molecules identified in the binding assay are then tested for antagonist or agonist activity in in vivo tissue culture or animal models that are well known in the art. In brief, the molecules are titrated into a plurality of cell cultures or animals and then tested for either cell/animal death or prolonged survival of the animal/cells.

[0211] The binding molecules thus identified may be complexed with toxins, e.g., ricin or cholera, or with other compounds that are toxic to cells such as radioisotopes. The toxin-binding molecule complex is then targeted to a tumor or other cell by the specificity of the binding molecule for a polypeptide of the invention. Alternatively, the binding molecules may be complexed with imaging agents for targeting and imaging purposes.

ASSAY FOR RECEPTOR ACTIVITY

[0212] The invention also provides methods to detect specific binding of a polypeptide e.g. a ligand or a receptor. The art provides numerous assays particularly useful for identifying previously unknown binding partners for receptor polypeptides of the invention. For example, expression cloning using mammalian or bacterial cells, or dihybrid screening assays can be used to identify polynucleotides encoding binding partners. As another example, affinity chromatography with the appropriate immobilized polypeptide of the invention can be used to isolate polypeptides that recognize and bind polypeptides of the invention. There are a number of different libraries used for the identification of compounds, and in particular small molecules, that modulate (i.e., increase or decrease) biological activity of a polypeptide of the invention. Ligands for receptor polypeptides of the invention can also be identified by adding exogenous ligands, or cocktails of ligands to two cells populations that are genetically identical except for the expression of the receptor of the invention: one cell population expresses the receptor of the invention whereas the other does not. The response of the two cell populations to the addition of ligands(s) are then compared. Alternatively, an expression library can be co-expressed with the polypeptide of the invention in cells and assayed for an autocrine response to identify potential ligand(s). As still another example, BlAcore assays, gel overlay assays, or other methods known in the art can be used to identify binding partner polypeptides, including, (1) organic and inorganic chemical libraries, (2) natural product libraries, and (3) combinatorial libraries comprised of random peptides, oligonucleotides or organic molecules.

[0213] The role of downstream intracellular signaling molecules in the signaling cascade of the polypeptide of the invention can be determined. For example, a chimeric protein in which the cytoplasmic domain of the polypeptide of the invention is fused to the extracellular portion of a protein, whose ligand has been identified, is produced in a host cell. The cell is then incubated with the ligand specific for the extracellular portion of the chimeric protein, thereby activating the chimeric receptor. Known downstream proteins involved in intracellular signaling can then be assayed for expected modifications i.e. phosphorylation. Other methods known to those in the art can also be used to identify signaling molecules involved in receptor activity.

ANTI-INFLAMMATORY ACTIVITY

[0214] Compositions of the present invention may also exhibit anti-inflammatory activity. The anti-inflammatory activity may be achieved by providing a stimulus to cells involved in the inflammatory response, by inhibiting or promoting cell-cell interactions (such as, for example, cell adhesion), by inhibiting or promoting chemotaxis of cells involved in the inflammatory process, inhibiting or promoting cell extravasation, or by stimulating or suppressing production of other factors which more directly inhibit or promote an inflammatory response. Compositions with such activities can be used to treat inflammatory conditions including chronic or acute conditions), including without limitation intimation associated with infection (such as septic shock, sepsis or systemic inflammatory response syndrome (SIRS)), ischemia-reperfusion injury, endotoxin lethality, arthritis, complement-mediated hyperacute rejection, nephritis, cytokine or chemokine-induced lung injury, inflammatory bowel disease, Crohn's disease or resulting from over production of cytokines such as TNF or IL-1. Compositions of the invention may also be useful to treat anaphylaxis and hypersensitivity to an antigenic substance or material. Compositions of this invention may be utilized to prevent or treat conditions such as, but not limited to, sepsis, acute pancreatitis, endotoxin shock, cytokine induced shock, rheumatoid arthritis, chronic inflammatory arthritis, pancreatic cell damage from diabetes mellitus type 1, graft versus host disease, inflammatory bowel disease, inflamation associated with pulmonary disease, other autoimmune disease or inflammatory disease, an antiproliferative agent such as for acute or chronic mylegenous leukemia or in the prevention of premature labor secondary to intrauterine infections.

LEUKEMIAS

[0215] Leukemias and related disorders may be treated or prevented by administration of a therapeutic that promotes or inhibits function of the polynucleotides and/or polypeptides of the invention. Such leukemias and related disorders include but are not limited to acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia, mycloblastic, promyelocytic, myelomonocytic, monocytic, erythroleukemia, chronic leukemia, chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia (for a review of such disorders, see Fishman et al., 1985, Medicine, 2d Ed., J. B. Lippincott Co., Philadelphia).

NERVOUS SYSTEM DISORDERS

[0216] Nervous system disorders, involving cell types which can be tested for efficacy of intervention with compounds that modulate the activity of the polynucleotides and/or polypeptides of the invention, and which can be treated upon thus observing an indication of therapeutic utility, include but are not limited to nervous system injuries, and diseases or disorders which result in either a disconnection of axons, a diminution or degeneration of neurons, or demyelination. Nervous system lesions which may be treated in a patient (including human and non-human mammalian patients) according to the invention include but are not limited to the following lesions of either the central (including spinal cord, brain) or peripheral nervous systems:

[0217] (i) traumatic lesions, including lesions caused by physical injury or associated with surgery, for example, lesions which sever a portion of the nervous system, or compression injuries;

[0218] (ii) ischemic lesions, in which a lack of oxygen in a portion of the nervous system results in neuronal injury or death, including cerebral infarction or ischemia, or spinal cord infarction or ischemia;

[0219] (iii) infectious lesions, in which a portion of the nervous system is destroyed or injured as a result of infection, for example, by an abscess or associated with infection by human immunodeficiency virus, herpes zoster, or herpes simplex virus or with Lyme disease, tuberculosis, syphilis;

[0220] (iv) degenerative lesions, in which a portion of the nervous system is destroyed or injured as a result of a degenerative process including but not limited to degeneration associated with Parkinson's disease, Alzheimer's disease, Huntington's chorea, or amyotrophic lateral sclerosis;

[0221] (v) lesions associated with nutritional diseases or disorders, in which a portion of the nervous system is destroyed or injured by a nutritional disorder or disorder of metabolism including but not limited to, vitamin B12 deficiency, folic acid deficiency, Wernicke disease, tobacco-alcohol amblyopia, Marchiafava-Bignami disease (primary degeneration of the corpus callosum), and alcoholic cerebellar degeneration;

[0222] (vi) neurological lesions associated with systemic diseases including but not limited to diabetes (diabetic neuropathy, Bell's palsy), systemic lupus erythematosus, carcinoma, or sarcoidosis;

[0223] (vii) lesions caused by toxic substances including alcohol, lead, or particular neurotoxins; and

[0224] (viii) demyelinated lesions in which a portion of the nervous system is destroyed or injured by a demyelinating disease including but not limited to multiple sclerosis, human immunodeficiency virus-associated myelopathy, transverse myelopathy or various etiologies, progressive multifocal leukoencephalopathy, and central pontine myelinolysis.

[0225] Therapeutics which are useful according to the invention for treatment of a nervous system disorder may be selected by testing for biological activity in promoting the survival or differentiation of neurons. For example, and not by way of limitation, therapeutics which elicit any of the following effects may be useful according to the invention:

[0226] (i) increased survival time of neurons in culture;

[0227] (ii) increased sprouting of neurons in culture or in vivo;

[0228] (iii) increased production of a neuron-associated molecule in culture or in vivo, e.g., choline acetyltransferase or acetylcholinesterase with respect to motor neurons; or

[0229] (iv) decreased symptoms of neuron dysfunction in vivo.

[0230] Such effects may be measured by any method known in the art. In preferred, non-limiting embodiments, increased survival of neurons may be measured by the method set forth in Arakawa et al. (1990, J. Neurosci. 10:3507-3515); increased sprouting of neurons may be detected by methods set forth in Pestronk et al. (1980, Exp. Neurol. 70:65-82) or Brown et al. (1981, Ann. Rev. Neurosci. 4:17-42); increased production of neuron-associated molecules may be measured by bioassay, enzymatic assay, antibody binding, Northern blot assay, etc., depending on the molecule to be measured; and motor neuron dysfunction may be measured by assessing the physical manifestation of motor neuron disorder, e.g., weakness, motor neuron conduction velocity, or functional disability.

[0231] In specific embodiments, motor neuron disorders that may be treated according to the invention include but are not limited to disorders such as infarction, infection, exposure to toxin, trauma, surgical damage, degenerative disease or malignancy that may affect motor neurons as well as other components of the nervous system, as well as disorders that selectively affect neurons such as amyotrophic lateral sclerosis, and including but not limited to progressive spinal muscular atrophy, progressive bulbar palsy, primary lateral sclerosis, infantile and juvenile muscular atrophy, progressive bulbar paralysis of childhood (Fazio-Londe syndrome), poliomyelitis and the post polio syndrome, and Hereditary Motorsensory Neuropathy (Charcot-Marie-Tooth Disease).

OTHER ACTIVITIES

[0232] A polypeptide of the invention may also exhibit one or more of the following additional activities or effects: inhibiting the growth, infection or function of, or killing, infectious agents, including, without limitation, bacteria, viruses, fungi and other parasites; effecting (suppressing or enhancing) bodily characteristics, including, without limitation, height, weight, hair color, eye color, skin, fat to lean ratio or other tissue pigmentation, or organ or body part size or shape (such as, for example, breast augmentation or diminution, change in bone form or shape); effecting biorhythms or circadian cycles or rhythmns; effecting the fertility of male or female subjects; effecting the metabolism, catabolism, anabolism, processing, utilization, storage or elimination of dietary fat, lipid, protein, carbohydrate, vitamins, minerals, co-factors or other nutritional factors or component(s); effecting behavioral characteristics, including, without limitation, appetite, libido, stress, cognition (including cognitive disorders), depression (including depressive disorders) and violent behaviors; providing analgesic effects or other pain reducing effects; promoting differentiation and growth of embryonic stem cells in lineages other than hematopoietic lineages; hormonal or endocrine activity; in the case of enzymes, correcting deficiencies of the enzyme and treating deficiency-related diseases; treatment of hyperproliferative disorders (such as, for example, psoriasis); immunoglobulin-like activity (such as, for example, the ability to bind antigens or complement); and the ability to act as an antigen in a vaccine composition to raise an immune response against such protein or another material or entity which is cross-reactive with such protein.

IDENTIFICATION OF POLYMORPHISMS

[0233] The demonstration of polymorphisms makes possible the identification of such polymorphisms in human subjects and the pharnacogenetic use of this information for diagnosis and treatment. Such polymorphisms may be associated with, e.g., differential predisposition or susceptibility to various disease states (such as disorders involving inflammation or immune response) or a differential response to drug administration, and this genetic information can be used to tailor preventive or therapeutic treatment appropriately. For example, the existence of a polymorphism associated with a predisposition to inflammation or autoimmune disease makes possible the diagnosis of this condition in humans by identifying the presence of the polymorphism.

[0234] Polymorphisms can be identified in a variety of ways known in the art which all generally involve obtaining a sample from a patient, analyzing DNA from the sample, optionally involving isolation or amplification of the DNA, and identifying the presence of the polymorphism in the DNA. For example, PCR may be used to amplify an appropriate fragment of genomic DNA which may then be sequenced. Alternatively, the DNA may be subjected to allele-specific oligonucleotide hybridization (in which appropriate oligonucleotides are hybridized to the DNA under conditions permitting detection of a single base mismatch) or to a single nucleotide extension assay (in which an oligonucleotide that hybridizes immediately adjacent to the position of the polymorphism is extended with one or more labeled nucleotides). In addition, traditional restriction fragment length polymorphism analysis (using restriction enzymes that provide differential digestion of the genomic DNA depending on the presence or absence of the polymorphism) may be performed. Arrays with nucleotide sequences of the present invention can be used to detect polymorphisms. The array can comprise modified nucleotide sequences of the present invention in order to detect the nucleotide sequences of the present invention. In the alternative, any one of the nucleotide sequences of the present invention can be placed on the array to detect changes from those sequences.

[0235] Alternatively a polymorphism resulting in a change in the amino acid sequence could also be detected by detecting a corresponding change in amino acid sequence of the protein, e.g., by an antibody specific to the variant sequence.

ARTHRITIS AND INFLAMMATION

[0236] The immunosuppressive effects of the compositions of the invention against rheumatoid arthritis is determined in an experimental animal model system. The experimental model system is adjuvant induced arthritis in rats, and the protocol is described by J. Holoshitz, et at., 1983, Science, 219:56, or by B. Waksman et al., 1963, Int. Arch. Allergy Appl. Immunol., 23:129. Induction of the disease can be caused by a single injection, generally intradermally, of a suspension of killed Mycobacterium tuberculosis in complete Freund's adjuvant (CFA). The route of injection can vary, but rats may be injected at the base of the tail with an adjuvant mixture. The polypeptide is administered in phosphate buffered solution (PBS) at a dose of about 1-5 mg/kg. The control consists of administering PBS only.

[0237] The procedure for testing the effects of the test compound would consist of intradermally injecting killed Mycobacterium tuberculosis in CFA followed by immediately administering the test compound and subsequent treatment every other day until day 24. At 14, 15, 18, 20, 22, and 24 days after injection of Mycobacterium CFA, an overall arthritis score may be obtained as described by J. Holoskitz above. An analysis of the data would reveal that the test compound would have a dramatic affect on the swelling of the joints as measured by a decrease of the arthritis score.

THERAPEUTIC METHODS

[0238] The compositions (including polypeptide fragments, analogs, variants and antibodies or other binding partners or modulators including antisense polynucleotides) of the invention have numerous applications in a variety of therapeutic methods. Examples of therapeutic applications include, but are not limited to, those exemplified herein.

EXAMPLE

[0239] One embodiment of the invention is the administration of an effective amount of the polypeptides or other composition of the invention to individuals affected by a disease or disorder that can be modulated by regulating the peptides of the invention. While the mode of administration is not particularly important, parenteral administration is preferred. An exemplary mode of administration is to deliver an intravenous bolus. The dosage of the polypeptides or other composition of the invention will normally be determined by the prescribing physician. It is to be expected that the dosage will vary according to the age, weight, condition and response of the individual patient. Typically, the amount of polypeptide administered per dose will be in the range of about 0.01μg/kg to 100 mg/kg of body weight, with the preferred dose being about 0.1 μg/kg to 10 mg/kg of patient body weight. For parenteral administration, polypeptides of the invention will be formulated in an injectable form combined with a pharmaceutically acceptable parenteral vehicle. Such vehicles are well known in the art and examples include water, saline, Ringer's solution, dextrose solution, and solutions consisting of small amounts of the human serum albumin. The vehicle may contain minor amounts of additives that maintain the isotonicity and stability of the polypeptide or other active ingredient. The preparation of such solutions is within the skill of the art.

PHARMACEUTICAL FORMULATIONS AND ROUTES OF ADMINISTRATION

[0240] A protein or other composition of the present invention (from whatever source derived, including without limitation from recombinant and non-recombinant sources and including antibodies and other binding partners of the polypeptides of the invention) may be administered to a patient in need, by itself, or in pharmaceutical compositions where it is mixed with suitable carriers or excipient(s) at doses to treat or ameliorate a variety of disorders. Such a composition may optionally contain (in addition to protein or other active ingredient and a carrier) diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well known in the art. The term “pharmaceutically acceptable” means a non-toxic material that does not interfere with the effectiveness of the biological activity of the active ingredient(s). The characteristics of the carrier will depend on the route of administration. The pharmaceutical composition of the invention may also contain cytokines, lymphokines, or other hematopoietic factors such as M-CSF, GM-C SF, TNF, IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IFN, TN-F0, TNF1, TNF2, G-CSF, Meg-CSF, thrombopoietin, stem cell factor, and erythropoietin. In further compositions, proteins of the invention may be combined with other agents beneficial to the treatment of the disease or disorder in question. These agents include various growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factors (TGF-α and TGF-β), insulin-like growth factor (IGF), as well as cytokines described herein.

[0241] The pharmaceutical composition may further contain other agents which either enhance the activity of the protein or other active ingredient or complement its activity or use in treatment. Such additional factors and/or agents may be included in the pharmaceutical composition to produce a synergistic effect with protein or other active ingredient of the invention, or to minimize side effects. Conversely, protein or other active ingredient of the present invention may be included in formulations of the particular clotting factor, cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti- inflammatory agent to minimize side effects of the clotting factor, cytokine, lymphokine, other hematopoietic factor, thrombolytic or anti-thrombotic factor, or anti-inflammatory agent (such as IL-1Ra, IL-1 Hy1, IL-1 Hy2, anti-TNF, corticosteroids, immunosuppressive agents). A protein of the present invention may be active in multimers (e.g., heterodimers or homodimers) or complexes with itself or other proteins. As a result, pharmaceutical compositions of the invention may comprise a protein of the invention in such multimeric or complexed form.

[0242] As an alternative to being included in a pharmaceutical composition of the invention including a first protein, a second protein or a therapeutic agent may be concurrently administered with the first protein (e.g., at the same time, or at differing times provided that therapeutic concentrations of the combination of agents is achieved at the treatment site). Techniques for formulation and administration of the compounds of the instant application may be found in “Remington's Pharmaceutical Sciences,” Mack Publishing Co., Easton, Pa., latest edition. A therapeutically effective dose further refers to that amount of the compound sufficient to result in amelioration of symptoms, e.g., treatment, healing, prevention or amelioration of the relevant medical condition, or an increase in rate of treatment, healing, prevention or amelioration of such conditions. When applied to an individual active ingredient, administered alone, a therapeutically effective dose refers to that ingredient alone. When applied to a combination, a therapeutically effective dose refers to combined amounts of the active ingredients that result in the therapeutic effect, whether administered in combination, serially or simultaneously.

[0243] In practicing the method of treatment or use of the present invention, a therapeutically effective amount of protein or other active ingredient of the present invention is administered to a mammal having a condition to be treated. Protein or other active ingredient of the present invention may be administered in accordance with the method of the invention either alone or in combination with other therapies such as treatments employing cytokines, lymphokines or other hematopoietic factors. When co-administered with one or more cytokines, lymphokines or other hematopoietic factors, protein or other active ingredient of the present invention may be administered either simultaneously with the cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors, or sequentially. If administered sequentially, the attending physician will decide on the appropriate sequence of administering protein or other active ingredient of the present invention in combination with cytokine(s), lymphokine(s), other hematopoietic factor(s), thrombolytic or anti-thrombotic factors.

ROUTES OF ADMINISTRATION

[0244] Suitable routes of administration may, for example, include oral, rectal, transmucosal, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections. Administration of protein or other active ingredient of the present invention used in the pharmaceutical composition or to practice the method of the present invention can be carried out in a variety of conventional ways, such as oral ingestion, inhalation, topical application or cutaneous, subcutaneous, intraperitoneal, parenteral or intravenous injection. Intravenous administration to the patient is preferred.

[0245] Alternately, one may administer the compound in a local rather than systemic manner, for example, via injection of the compound directly into a arthritic joints or in fibrotic tissue, often in a depot or sustained release formulation. In order to prevent the scarring process frequently occurring as complication of glaucoma surgery, the compounds may be administered topically, for example, as eye drops. Furthermore, one may administer the drug in a targeted drug delivery system, for example, in a liposome coated with a specific antibody, targeting, for example, arthritic or fibrotic tissue. The liposomes will be targeted to and taken up selectively by the afflicted tissue.

[0246] The polypeptides of the invention are administered by any route that delivers an effective dosage to the desired site of action. The determination of a suitable route of administration and an effective dosage for a particular indication is within the level of skill in the art. Preferably for wound treatment, one administers the therapeutic compound directly to the site. Suitable dosage ranges for the polypeptides of the invention can be extrapolated from these dosages or from similar studies in appropriate animal models. Dosages can then be adjusted as necessary by the clinician to provide maximal therapeutic benefit.

COMPOSITIONS/FORMULATIONS

[0247] Pharmaceutical compositions for use in accordance with the present invention thus may be formulated in a conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries which facilitate processing of the active compounds into preparations which can be used pharmaceutically. These pharmaceutical compositions may be manufactured in a manner that is itself known, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes. Proper formulation is dependent upon the route of administration chosen. When a therapeutically effective amount of protein or other active ingredient of the present invention is administered orally, protein or other active ingredient of the present invention will be in the form of a tablet, capsule, powder, solution or elixir. When administered in tablet form, the pharmaceutical composition of the invention may additionally contain a solid carrier such as a gelatin or an adjuvant. The tablet, capsule, and powder contain from about 5 to 95% protein or other active ingredient of the present invention, and preferably from about 25 to 90% protein or other active ingredient of the present invention. When administered in liquid form, a liquid carrier such as water, petroleum, oils of animal or plant origin such as peanut oil, mineral oil, soybean oil, or sesame oil, or synthetic oils may be added. The liquid form of the pharmaceutical composition may further contain physiological saline solution, dextrose or other saccharide solution, or glycols such as ethylene glycol, propylene glycol or polyethylene glycol. When administered in liquid form, the pharmaceutical composition contains from about 0.5 to 90% by weight of protein or other active ingredient of the present invention, and preferably from about 1 to 50% protein or other active ingredient of the present invention.

[0248] When a therapeutically effective amount of protein or other active ingredient of the present invention is administered by intravenous, cutaneous or subcutaneous injection, protein or other active ingredient of the present invention will be in the form of a pyrogen-free, parenterally acceptable aqueous solution. The preparation of such parenterally acceptable protein or other active ingredient solutions, having due regard to pH, isotonicity, stability, and the like, is within the skill in the art. A preferred pharmaceutical composition for intravenous, cutaneous, or subcutaneous injection should contain, in addition to protein or other active ingredient of the present invention, an isotonic vehicle such as Sodium Chloride Injection, Ringer's Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, Lactated Ringer's Injection, or other vehicle as known in the art. The pharmaceutical composition of the present invention may also contain stabilizers, preservatives, buffers, antioxidants, or other additives known to those of skill in the art. For injection, the agents of the invention may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hanks's solution, Ringer's solution, or physiological saline buffer. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.

[0249] For oral administration, the compounds can be formulated readily by combining the active compounds with pharmnaceutically acceptable carriers well known in the art. Such carriers enable the compounds of the invention to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions and the like, for oral ingestion by a patient to be treated. Pharmaceutical preparations for oral use can be obtained from a solid excipient, optionally grinding a resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries, if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as the cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate. Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used, which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, and/or titanium dioxide, lacquer solutions, and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses.

[0250] Pharmaceutical preparations which can be used orally include push-fit capsules made of gelatin, as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules can contain the active ingredients in admixture with filler such as lactose, binders such as starches, and/or lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active compounds may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. All formulations for oral administration should be in dosages suitable for such administration. For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner.

[0251] For administration by inhalation, the compounds for use according to the present invention are conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebuliser, with the use of a suitable propellant, e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas. In the case of a pressurized aerosol the dosage unit may be determined by providing a valve to deliver a metered amount. Capsules and cartridges of, e.g., gelatin for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch. The compounds may be formulated for parenteral administration by injection, e.g., by bolus injection or continuous infusion. Formulations for injection may be presented in unit dosage form, e.g., in ampules or in multi-dose containers, with an added preservative. The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilizing and/or dispersing agents.

[0252] Pharmaceutical formulations for parenteral administration include aqueous solutions of the active compounds in water-soluble form. Additionally, suspensions of the active compounds may be prepared as appropriate oily injection suspensions. Suitable lipophilic solvents or vehicles include fatty oils such as sesame oil, or synthetic fatty acid esters, such as ethyl oleate or triglycerides, or liposomes. Aqueous injection suspensions may contain substances which increase the viscosity of the suspension, such as sodium carboxymethyl cellulose, sorbitol, or dextran. Optionally, the suspension may also contain suitable stabilizers or agents which increase the solubility of the compounds to allow for the preparation of highly concentrated solutions. Alternatively, the active ingredient may be in powder form for constitution with a suitable vehicle, e.g., sterile pyrogen-free water, before use.

[0253] The compounds may also be formulated in rectal compositions such as suppositories or retention enemas, e.g., containing conventional suppository bases such as cocoa butter or other glycerides. In addition to the formulations described previously, the compounds may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection. Thus, for example, the compounds may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.

[0254] A pharmaceutical carrier for the hydrophobic compounds of the invention is a co-solvent system comprising benzyl alcohol, a nonpolar surfactant, a water-miscible organic polymer, and an aqueous phase. The co-solvent system may be the VPD co-solvent system. VPD is a solution of 3% w/v benzyl alcohol, 8% w/v of the nonpolar surfactant polysorbate 80, and 65% w/v polyethylene glycol 300, made up to volume in absolute ethanol. The VPD co-solvent system (VPD:5W) consists of VPD diluted 1:1 with a 5% dextrose in water solution. This co-solvent system dissolves hydrophobic compounds well, and itself produces low toxicity upon systemic administration. Naturally, the proportions of a co-solvent system may be varied considerably without destroying its solubility and toxicity characteristics. Furthermore, the identity of the co-solvent components may be varied: for example, other low-toxicity nonpolar surfactants may be used instead of polysorbate 80; the fraction size of polyethylene glycol may be varied; other biocompatible polymers may replace polyethylene glycol, e.g. polyvinyl pyrrolidone; and other sugars or polysaccharides may substitute for dextrose. Alternatively, other delivery systems for hydrophobic pharmaceutical compounds may be employed. Liposomes and emulsions are well known examples of delivery vehicles or carriers for hydrophobic drugs. Certain organic solvents such as dimethylsulfoxide also may be employed, although usually at the cost of greater toxicity. Additionally, the compounds may be delivered using a sustained-release system, such as semipermeable matrices of solid hydrophobic polymers containing the therapeutic agent. Various types of sustained-release materials have been established and are well known by those skilled in the art. Sustained-release capsules may, depending on their chemical nature, release the compounds for a few weeks up to over 100 days. Depending on the chemical nature and the biological stability of the therapeutic reagent, additional strategies for protein or other active ingredient stabilization may be employed.

[0255] The pharmaceutical compositions also may comprise suitable solid or gel phase carriers or excipients. Examples of such carriers or excipients include but are not limited to calcium carbonate, calcium phosphate, various sugars, starches, cellulose derivatives, gelatin, and polymers such as polyethylene glycols. Many of the active ingredients of the invention may be provided as salts with pharmaceutically compatible counter ions. Such pharmaceutically acceptable base addition salts are those salts which retain the biological effectiveness and properties of the free acids and which are obtained by reaction with inorganic or organic bases such as sodium hydroxide, magnesium hydroxide, ammonia, trialkylamine, dialkylamine, monoalkylamine, dibasic amino acids, sodium acetate, potassium benzoate, triethanol amine and the like.

[0256] The pharmaceutical composition of the invention may be in the form of a complex of the protein(s) or other active ingredient(s) of present invention along with protein or peptide antigens. The protein and/or peptide antigen will deliver a stimulatory signal to both B and T lymphocytes. B lymphocytes will respond to antigen through their surface immunoglobulin receptor. T lymphocytes will respond to antigen through the T cell receptor (TCR) following presentation of the antigen by MHC proteins. MHC and structurally related proteins including those encoded by class I and class II MHC genes on host cells will serve to present the peptide antigen(s) to T lymphocytes. The antigen components could also be supplied as purified MHC-peptide complexes alone or with co-stimulatory molecules that can directly signal T cells. Alternatively antibodies able to bind surface immunoglobulin and other molecules on B cells as well as antibodies able to bind the TCR and other molecules on T cells can be combined with the pharmaceutical composition of the invention.

[0257] The pharmaceutical composition of the invention may be in the form of a liposome in which protein of the present invention is combined, in addition to other pharmaceutically acceptable carriers, with amphipathic agents such as lipids which exist in aggregated form as micelles, insoluble monolayers, liquid crystals, or lamellar layers in aqueous solution. Suitable lipids for liposomal formulation include, without limitation, monoglycerides, diglycerides, sulfatides, lysolecithins, phospholipids, saponin, bile acids, and the like. Preparation of such liposomal formulations is within the level of skill in the art, as disclosed, for example, in U.S. Pat. Nos. 4,235,871; 4,501,728; 4,837,028; and 4,737,323, all of which are incorporated herein by reference.

[0258] The amount of protein or other active ingredient of the present invention in the pharmaceutical composition of the present invention will depend upon the nature and severity of the condition being treated, and on the nature of prior treatments which the patient has undergone. Ultimately, the attending physician will decide the amount of protein or other active ingredient of the present invention with which to treat each individual patient. Initially, the attending physician will administer low doses of protein or other active ingredient of the present invention and observe the patient's response. Larger doses of protein or other active ingredient of the present invention may be administered until the optimal therapeutic effect is obtained for the patient, and at that point the dosage is not increased further. It is contemplated that the various pharmaceutical compositions used to practice the method of the present invention should contain about 0.01 μg to about 100 mg (preferably about 0.1 μg to about 10 mg, more preferably about 0.1 μg to about 1 mg) of protein or other active ingredient of the present invention per kg body weight. For compositions of the present invention which are useful for bone, cartilage, tendon or ligament regeneration, the therapeutic method includes administering the composition topically, systematically, or locally as an implant or device. When administered, the therapeutic composition for use in this invention is, of course, in a pyrogen-free, physiologically acceptable form. Further, the composition may desirably be encapsulated or injected in a viscous form for delivery to the site of bone, cartilage or tissue damage. Topical administration may be suitable for wound healing and tissue repair. Therapeutically useful agents other than a protein or other active ingredient of the invention which may also optionally be included in the composition as described above, may alternatively or additionally, be administered simultaneously or sequentially with the composition in the methods of the invention. Preferably for bone and/or cartilage formation, the composition would include a matrix capable of delivering the protein-containing or other active ingredient-containing composition to the site of bone and/or cartilage damage, providing a structure for the developing bone and cartilage and optimally capable of being resorbed into the body. Such matrices may be formed of materials presently in use for other implanted medical applications.

[0259] The choice of matrix material is based on biocompatibility, biodegradability, mechanical properties, cosmetic appearance and interface properties. The particular application of the compositions will define the appropriate formulation. Potential matrices for the compositions may be biodegradable and chemically defined calcium sulfate, tricalcium phosphate, hydroxyapatite, polylactic acid, polyglycolic acid and polyanhydrides. Other potential materials are biodegradable and biologically well-defined, such as bone or dermal collagen. Further matrices are comprised of pure proteins or extracellular matrix components. Other potential matrices are nonbiodegradable and chemically defined, such as sintered hydroxyapatite, bioglass, aluminates, or other ceramics. Matrices may be comprised of combinations of any of the above mentioned types of material, such as polylactic acid and hydroxyapatite or collagen and tricalcium phosphate. The bioceramics may be altered in composition, such as in calcium-aluminate-phosphate and processing to alter pore size, particle size, particle shape, and biodegradability. Presently preferred is a 50:50 (mole weight) copolymer of lactic acid and glycolic acid in the form of porous particles having diameters ranging from 150 to 800 microns. In some applications, it will be useful to utilize a sequestering agent, such as carboxymethyl cellulose or autologous blood clot, to prevent the protein compositions from disassociating from the matrix.

[0260] A preferred family of sequestering agents is cellulosic materials such as alkylcelluloses (including hydroxyalkylcelluloses), including methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropyl-methylcellulose, and carboxymethylcellulose, the most preferred being cationic salts of carboxymethylcellulose (CMC). Other preferred sequestering agents include hyaluronic acid, sodium alginate, poly(ethylene glycol), polyoxyethylene oxide, carboxyvinyl polymer and poly(vinyl alcohol). The amount of sequestering agent useful herein is 0.5-20 wt %, preferably 1-10 wt % based on total formulation weight, which represents the amount necessary to prevent desorption of the protein from the polymer matrix and to provide appropriate handling of the composition, yet not so much that the progenitor cells are prevented from infiltrating the matrix, thereby providing the protein the opportunity to assist the osteogenic activity of the progenitor cells. In further compositions, proteins or other active ingredients of the invention may be combined with other agents beneficial to the treatment of the bone and/or cartilage defect, wound, or tissue in question. These agents include various growth factors such as epidermal growth factor (EGF), platelet derived growth factor (PDGF), transforming growth factors (TGF-α and TGF-β), and insulin-like growth factor (IGF).

[0261] The therapeutic compositions are also presently valuable for veterinary applications. Particularly domestic animals and thoroughbred horses, in addition to humans, are desired patients for such treatment with proteins or other active ingredients of the present invention. The dosage regimen of a protein-containing pharmaceutical composition to be used in tissue regeneration will be determined by the attending physician considering various factors which modify the action of the proteins, e.g., amount of tissue weight desired to be formed, the site of damage, the condition of the damaged tissue, the size of a wound, type of damaged tissue (e.g., bone), the patient's age, sex, and diet, the severity of any infection, time of administration and other clinical factors. The dosage may vary with the type of matrix used in the reconstitution and with inclusion of other proteins in the pharmaceutical composition. For example, the addition of other known growth factors, such as IGF I (insulin like growth factor I), to the final composition, may also effect the dosage. Progress can be monitored by periodic assessment of tissue/bone growth and/or repair, for example, X-rays, histomorphometric determinations and tetracycline labeling.

[0262] Polynucleotides of the present invention can also be used for gene therapy. Such polynucleotides can be introduced either in vivo or ex vivo into cells for expression in a mammalian subject. Polynucleotides of the invention may also be administered by other known methods for introduction of nucleic acid into a cell or organism (including, without limitation, in the form of viral vectors or naked DNA). Cells may also be cultured ex vivo in the presence of proteins of the present invention in order to proliferate or to produce a desired effect on or activity in such cells. Treated cells can then be introduced in vivo for therapeutic purposes.

EFFECTIVE DOSAGE

[0263] Pharmaceutical compositions suitable for use in the present invention include compositions wherein the active ingredients are contained in an effective amount to achieve its intended purpose. More specifically, a therapeutically effective amount means an amount effective to prevent development of or to alleviate the existing symptoms of the subject being treated. Determination of the effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein. For any compound used in the method of the invention, the therapeutically effective dose can be estimated initially from appropriate in vitro assays. For example, a dose can be formulated in animal models to achieve a circulating concentration range that can be used to more accurately determine useful doses in humans. For example, a dose can be formulated in animal models to achieve a circulating concentration range that includes the IC₅₀ as determined in cell culture (i.e., the concentration of the test compound which achieves a half-maximal inhibition of the protein's biological activity). Such information can be used to more accurately determine useful doses in humans.

[0264] A therapeutically effective dose refers to that amount of the compound that results in amelioration of symptoms or a prolongation of survival in a patient. Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD₅₀ (the dose lethal to 50% of the population) and the ED₅₀ (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and it can be expressed as the ratio between LD₅₀ and ED₅₀. Compounds which exhibit high therapeutic indices are preferred. The data obtained from these cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage of such compounds lies preferably within a range of circulating concentrations that include the ED₅₀ with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. See, e.g., Fingl et al., 1975, in “The Pharmacological Basis of Therapeutics”, Ch. 1 p.1. Dosage amount and interval may be adjusted individually to provide plasma levels of the active moiety which are sufficient to maintain the desired effects, or minimal effective concentration (MEC). The MEC will vary for each compound but can be estimated from in vitro data. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. However, HPLC assays or bioassays can be used to determine plasma concentrations.

[0265] Dosage intervals can also be determined using MEC value. Compounds should be administered using a regimen which maintains plasma levels above the MEC for 10-90% of the time, preferably between 30-90% and most preferably between 50-90%. In cases of local administration or selective uptake, the effective local concentration of the drug may not be related to plasma concentration.

[0266] An exemplary dosage regimen for polypeptides or other compositions of the invention will be in the range of about 0.01 μg/kg to 100 mg/kg of body weight daily, with the preferred dose being about 0.1 μg/kg to 25 mg/kg of patient body weight daily, varying in adults and children. Dosing may be once daily, or equivalent doses may be delivered at longer or shorter intervals.

[0267] The amount of composition administered will, of course, be dependent on the subject being treated, on the subject's age and weight, the severity of the affliction, the manner of administration and the judgment of the prescribing physician.

PACKAGING

[0268] The compositions may, if desired, be presented in a pack or dispenser device which may contain one or more unit dosage forms containing the active ingredient. The pack may, for example, comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. Compositions comprising a compound of the invention formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition.

ANTIBODIES

[0269] Another aspect of the invention is an antibody that specifically binds the polypeptide of the invention. Such antibodies include monoclonal and polyclonal antibodies, single chain antibodies, chimeric antibodies, bifunctional/bispecific antibodies, humanized antibodies, human antibodies, and complementary determining region (CDR)-grafted antibodies, including compounds which include CDR and/or antigen-binding sequences, which specifically recognize a polypeptide of the invention. Preferred antibodies of the invention are human antibodies which are produced and identified according to methods described in WO93/11236, published Jun. 20, 1993, which is incorporated herein by reference in its entirety. Antibody fragments, including Fab, Fab′, F(ab′)₂, and F_(v), are also provided by the invention. The term “specific for” indicates that the variable regions of the antibodies of the invention recognize and bind polypeptides of the invention exclusively (i.e., able to distinguish the polypeptide of the invention from other similar polypeptides despite sequence identity, homology, or similarity found in the family of polypeptides), but may also interact with other proteins (for example, S. aureus protein A or other antibodies in ELISA techniques) through interactions with sequences outside the variable region of the antibodies, and in particular, in the constant region of the molecule. Screening assays to determine binding specificity of an antibody of the invention are well known and routinely practiced in the art. For a comprehensive discussion of such assays, see Harlow et al. (Eds), Antibodies A Laboratory Manual; Cold Spring Harbor Laboratory; Cold Spring Harbor, N.Y. (1988), Chapter 6. Antibodies that recognize and bind fragments of the polypeptides of the invention are also contemplated, provided that the antibodies are first and foremost specific for, as defined above, fall length polypeptides of the invention. As with antibodies that are specific for full length polypeptides of the invention, antibodies of the invention that recognize fragments are those which can distinguish polypeptides from the same family of polypeptides despite inherent sequence identity, homology, or similarity found in the family of proteins. Antibodies of the invention can be produced using any method well known and routinely practiced in the art.

[0270] Non-human antibodies may be humanized by any methods known in the art. In one method, the non-human CDRs are inserted into a human antibody or consensus antibody framework sequence. Further changes can then be introduced into the antibody framework to modulate affinity or immunogenicity.

[0271] Antibodies of the invention are useful for, for example, therapeutic purposes (by modulating activity of a polypeptide of the invention), diagnostic purposes to detect or quantitate a polypeptide of the invention, as well as purification of a polypeptide of the invention. Kits comprising an antibody of the invention for any of the purposes described herein are also comprehended. In general, a kit of the invention also includes a control antigen for which the antibody is immunospecific. The invention farther provides a hybridoma that produces an antibody according to the invention. Antibodies of the invention are useful for detection and/or purification of the polypeptides of the invention.

[0272] Polypeptides of the invention may also be used to immunize animals to obtain polyclonal and monoclonal antibodies which specifically react with the protein. Such antibodies may be obtained using either the entire protein or fragments thereof as an immunogen. The peptide immunogens additionally may contain a cysteine residue at the carboxyl terminus, and are conjugated to a hapten such as keyhole limpet hemocyanin (KLH). Methods for synthesizing such peptides are known in the art, for example, as in R. P. Merrifield, J. Amer. Chem. Soc. 85, 2149-2154 (1963); J. L. Krstenansky, et al., FEBS Lett. 211, 10 (1987).

[0273] Monoclonal antibodies binding to the protein of the invention may be useful diagnostic agents for the immunodetection of the protein. Neutralizing monoclonal antibodies binding to the protein may also be useful therapeutics for both conditions associated with the protein and also in the treatment of some forms of cancer where abnormal expression of the protein is involved. In the case of cancerous cells or leukemic cells, neutralizing monoclonal antibodies against the protein may be useful in detecting and preventing the metastatic spread of the cancerous cells, which may be mediated by the protein. In general, techniques for preparing polyclonal and monoclonal antibodies as well as hybridomas capable of producing the desired antibody are well known in the art (Campbell, A. M., Monoclonal Antibodies Technology: Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1984); St. Groth et al., J. Immunol. 35:1-21 (1990); Kohler and Milstein, Nature 256:495-497 (1975)), the trioma technique, the human B-cell hybridoma technique (Kozbor et al., Inununology Today 4:72 (1983); Cole et al., in Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc. (1985), pp. 77-96).

[0274] Any animal (mouse, rabbit, etc.) which is known to produce antibodies can be immunized with a peptide or polypeptide of the invention. Methods for immunization are well known in the art. Such methods include subcutaneous or intraperitoneal injection of the polypeptide. One skilled in the art will recognize that the amount of the protein encoded by the ORF of the present invention used for immunization will vary based on the animal which is immunized, the antigenicity of the peptide and the site of injection. The protein that is used as an immunogen may be modified or administered in an adjuvant in order to increase the protein's antigenicity. Methods of increasing the antigenicity of a protein are well known in the art and include, but are not limited to, coupling the antigen with a heterologous protein (such as globulin or P-galactosidase) or through the inclusion of an adjuvant during immunization.

[0275] For monoclonal antibodies, spleen cells from the immunized animals are removed, fused with myeloma cells, such as SP2/0-Ag14 myeloma cells, and allowed to become monoclonal antibody producing hybridoma cells. Any one of a number of methods well known in the art can be used to identify the hybridoma cell which produces an antibody with the desired characteristics. These include screening the hybridomas with an ELISA assay, Western blot analysis, or radioimmunoassay (Lutz et al., Exp. Cell Research. 175:109-124 (1988)). Hybridomas secreting the desired antibodies are cloned and the class and subclass is determined using procedures known in the art (Campbell, A. M., Monoclonal Antibody Technology: Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1984)). Techniques described for the production of single chain antibodies (U.S. Pat. 4,946,778) can be adapted to produce single chain antibodies to proteins of the present invention.

[0276] For polyclonal antibodies, antibody-containing antiserum is isolated from the immunized animal and is screened for the presence of antibodies with the desired specificity using one of the above-described procedures. The present invention further provides the above-described antibodies in delectably labeled form. Antibodies can be delectably labeled through the use of radioisotopes, affinity labels (such as biotin, avidin, etc.), enzymatic labels (such as horseradish peroxidase, alkaline phosphatase, etc.) fluorescent labels (such as FITC or rhodamine, etc.), paramagnetic atoms, etc. Procedures for accomplishing such labeling are well-known in the art, for example, see (Stemberger, L. A. et al., J. Histochem. Cytochem. 18:315 (1970); Bayer, E. A. et al., Meth. Enzym. 62:308 (1979); Engval, E. et al., Inununol. 109:129 (1972); Goding, J. W. J. Immunol. Meth. 13:215 (1976)).

[0277] The labeled antibodies of the present invention can be used for in vitro, in vivo, and in situ assays to identify cells or tissues in which a fragment of the polypeptide of interest is expressed. The antibodies may also be used directly in therapies or other diagnostics. The present invention further provides the above-described antibodies immobilized on a solid support. Examples of such solid supports include plastics such as polycarbonate, complex carbohydrates such as agarose and Sepharose®, acrylic resins and such as polyacrylamide and latex beads. Techniques for coupling antibodies to such solid supports are well known in the art (Weir, D. M. et al., “Handbook of Experimental Immunology” 4th Ed., Blackwell Scientific Publications, Oxford, England, Chapter 10 (1986); Jacoby, W. D. et al., Meth. Enzym. 34 Academic Press, N.Y. (1974)). The immobilized antibodies of the present invention can be used for in vitro, in vivo, and in situ assays as well as for immuno-affinity purification of the proteins of the present invention.

COMPUTER READABLE SEQUENCES

[0278] In one application of this embodiment, a nucleotide sequence of the present invention can be recorded on computer readable media. As used herein, “computer readable media” refers to any medium which can be read and accessed directly by a computer. Such media include, but are not limited to: magnetic storage media, such as floppy discs, hard disc storage medium, and magnetic tape; optical storage media such as CD-ROM; electrical storage media such as RAM and ROM; and hybrids of these categories such as magnetic/optical storage media. A skilled artisan can readily appreciate how any of the presently known computer readable mediums can be used to create a manufacture comprising computer readable medium having recorded thereon a nucleotide sequence of the present invention. As used herein, “recorded” refers to a process for storing information on computer readable medium. A skilled artisan can readily adopt any of the presently known methods for recording information on computer readable medium to generate manufactures comprising the nucleotide sequence information of the present invention.

[0279] A variety of data storage structures are available to a skilled artisan for creating a computer readable medium having recorded thereon a nucleotide sequence of the present invention. The choice of the data storage structure will generally be based on the means chosen to access the stored information. In addition, a variety of data processor programs and formats can be used to store the nucleotide sequence information of the present invention on computer readable medium. The sequence information can be represented in a word processing text file, formatted in commercially-available software such as WordPerfect and Microsoft Word, or represented in the form of an ASCII file, stored in a database application, such as DB2, Sybase, Oracle, or the like. A skilled artisan can readily adapt any number of data processor structuring formats (e.g. text file or database) in order to obtain computer readable medium having recorded thereon the nucleotide sequence information of the present invention.

[0280] By providing any of the nucleotide sequences SEQ ID NOs: 1-91 or a representative fragment thereof; or a nucleotide sequence at least 95% identical to any of the nucleotide sequences of SEQ ID NOs: 1-91 in computer readable form, a skilled artisan can routinely access the sequence information for a variety of purposes. Computer software is publicly available which allows a skilled artisan to access sequence information provided in a computer readable medium. The examples which follow demonstrate how software which implements the BLAST (Altschul et al., J. Mol. Biol. 215:403-410 (1990)) and BLAZE (Brutlag et al., Comp. Chem. 17:203-207 (1993)) search algorithms on a Sybase system is used to identify open reading frames (ORFs) within a nucleic acid sequence. Such ORFs may be protein encoding fragments and may be useful in producing commercially important proteins such as enzymes used in fermentation reactions and in the production of commercially useful metabolites.

[0281] As used herein, “a computer-based system” refers to the hardware means, software means, and data storage means used to analyze the nucleotide sequence information of the present invention. The minimum hardware means of the computer-based systems of the present invention comprises a central processing unit (CPU), input means, output means, and data storage means. A skilled artisan can readily appreciate that any one of the currently available computer-based systems are suitable for use in the present invention. As stated above, the computer-based systems of the present invention comprise a data storage means having stored therein a nucleotide sequence of the present invention and the necessary hardware means and software means for supporting and implementing a search means. As used herein, “data storage means” refers to memory which can store nucleotide sequence information of the present invention, or a memory access means which can access manufactures having recorded thereon the nucleotide sequence information of the present invention.

[0282] As used herein, “search means” refers to one or more programs which are implemented on the computer-based system to compare a target sequence or target structural motif with the sequence information stored within the data storage means. Search means are used to identify fragments or regions of a known sequence which match a particular target sequence or target motif. A variety of known algorithms are disclosed publicly and a variety of commercially available software for conducting search means are and can be used in the computer-based systems of the present invention. Examples of such software includes, but is not limited to, Smith-Waterman, MacPattem (EMBL), BLASTN and BLASTA (NPOLYPEPTIDEIA). A skilled artisan can readily recognize that any one of the available algorithms or implementing software packages for conducting homology searches can be adapted for use in the present computer-based systems. As used herein, a “target sequence” can be any nucleic acid or amino acid sequence of six or more nucleotides or two or more amino acids. A skilled artisan can readily recognize that the longer a target sequence is, the less likely a target sequence will be present as a random occurrence in the database. The most preferred sequence length of a target sequence is from about 10 to 300 amino acids, more preferably from about 30, to 100 nucleotide residues. However, it is well recognized that searches for commercially important fragments, such as sequence fragments involved in gene expression and protein processing, may be of shorter length.

[0283] As used herein, “a target structural motif,” or “target motif,” refers to any rationally selected sequence or combination of sequences in which the sequencers) are chosen based on a three-dimensional configuration which is formed upon the folding of the target motif. There are a variety of target motifs known in the art. Protein target motifs include, but are not limited to, enzyme active sites and signal sequences. Nucleic acid target motifs include, but are not limited to, promoter sequences, hairpin structures and inducible expression elements (protein binding sequences).

TRIPLE HELIX FORMATION

[0284] In addition, the fragments of the present invention, as broadly described, can be used to control gene expression through triple helix formation or anti sense DNA or RNA, both of which methods are based on the binding of a polynucleotide sequence to DNA or RNA. Polynucleotides suitable for use in these methods are preferably 20 to 40 bases in length and are designed to be complementary to a region of the gene involved in transcription (triple helix-see Lee et al., Nucl. Acids Res. 6:3073 (1979); Cooney et al., Science 15241:456 (1988); and Dervan et al., Science 251:1360 (1991)) or to the mRNA itself (antisense-Olmno, J. Neurochem. 56:560 (1991); Oligodeoxynucleotides as Antisense Inibitors of Gene Expression, CRC Press, Boca Raton, Fla. (1988)), Triple helix-formation optimally results in a shut-off of RNA transcription from DNA, while anitisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques have been demonstrated to be effective in model systems. Information contained in the sequences of the present invention is necessary for the design of an antisense or triple helix oligonucleotide.

DIAGNOSTIC ASSAYS AND KITS

[0285] The present invention further provides methods to identify the presence or expression of one of the ORFs of the present invention, or homolog thereof, in a test sample, using a nucleic acid probe or antibodies of the present invention, optionally conjugated or otherwise associated with a suitable label.

[0286] In general, methods for detecting a polynucleotide of the invention can comprise contacting a sample with a compound that binds to and forms a complex with the polynucleotide for a period sufficient to form the complex, and detecting the complex, so that if a complex is detected, a polynucleotide of the invention is detected in the sample. Such methods can also comprise contacting a sample under stringent hybridization conditions with nucleic acid primers that anneal to a polynucleotide of the invention under such conditions, and amplifying annealed polynucleotides, so that if a polynucleotide is amplified, a polynucleotide of the invention is detected in the sample.

[0287] In general, methods for detecting a polypeptide of the invention can comprise contacting a sample with a compound that binds to and forms a complex with the polypeptide for a period sufficient to form the complex, and detecting the complex, so that if a complex is detected, a polypeptide of the invention is detected in the sample.

[0288] In detail, such methods comprise incubating a test sample with one or more of the antibodies or one or more of the nucleic acid probes of the present invention and assaying for binding of the nucleic acid probes or antibodies to components within the test sample.

[0289] Conditions for incubating a nucleic acid probe or antibody with a test sample vary. Incubation conditions depend on the format employed in the assay, the detection methods employed, and the type and nature of the nucleic acid probe or antibody used in the assay. One skilled in the art will recognize that any one of the commonly available hybridization, amplification or immunological assay formats can readily be adapted to employ the nucleic acid probes or antibodies of the present invention. Examples of such assays can be found in Chard, T., An Introduction to Radioimmunoassay and Related Techniques, Elsevier Science Publishers, Amsterdam, The Netherlands (1986); Bullock, G. R. et al., Techniques in Immunocytochemistry, Academic Press, Orlando, Fla. Vol. 1 (1982), Vol. 2 (1983), Vol. 3 (1985); Tijssen, P., Practice and Theory of immunoassays: Laboratory Techniques in Biochemistry and Molecular Biology, Elsevier Science Publishers, Amsterdam, The Netherlands (1985). The test samples of the present invention include cells, protein or membrane extracts of cells, or biological fluids such as sputum, blood, serum, plasma, or urine. The test sample used in the above-described method will vary based on the assay format, nature of the detection method and the tissues, cells or extracts used as the sample to be assayed. Methods for preparing protein extracts or membrane extracts of cells are well known in the art and can be readily be adapted in order to obtain a sample which is compatible with the system utilized.

[0290] In another embodiment of the present invention, kits are provided which contain the necessary reagents to carry out the assays of the present invention. Specifically, the invention provides a compartment kit to receive, in close confinement, one or more containers which comprises: (a) a first container comprising one of the probes or antibodies of the present invention; and (b) one or more other containers comprising one or more of the following: wash reagents, reagents capable of detecting presence of a bound probe or antibody.

[0291] In detail, a compartment kit includes any kit in which reagents are contained in separate containers. Such containers include small glass containers, plastic containers or strips of plastic or paper. Such containers allows one to efficiently transfer reagents from one compartment to another compartment such that the samples and reagents are not cross-contaminated, and the agents or solutions of each container can be added in a quantitative fashion from one compartment to another. Such containers will include a container which will accept the test sample, a container which contains the antibodies used in the assay, containers which contain wash reagents (such as phosphate buffered saline, Tris-buffers, etc.), and containers which contain the reagents used to detect the bound antibody or probe. Types of detection reagents include labeled nucleic acid probes, labeled secondary antibodies, or in the alternative, if the primary antibody is labeled, the enzymatic, or antibody binding reagents which are capable of reacting with the labeled antibody. One skilled in the art will readily recognize that the disclosed probes and antibodies of the present invention can be readily incorporated into one of the established kit formats which are well known in the art.

MEDICAL IMAGING

[0292] The novel polypeptides and binding partners of the invention are useful in medical imaging of sites expressing the molecules of the invention (e.g., where the polypeptide of the invention is involved in the immune response, for imaging sites of inflammation or infection). See, e.g., Kunkel et al., U.S. Pat. NO. 5,413,778. Such . methods involve chemical attachment of a labeling or imaging agent, administration of the labeled polypeptide to a subject in a pharmaceutically acceptable carrier, and imaging the labeled polypeptide in vivo at the target site.

SCREENING ASSAYS

[0293] Using the isolated proteins and polynucleotides of the invention, the present invention further provides methods of obtaining and identifying agents which bind to a polypeptide encoded by an ORF corresponding to any of the nucleotide sequences set forth in SEQ ID NOs: 1-91, or bind to a specific domain of the polypeptide encoded by the nucleic acid. In detail, said method comprises the steps of:

[0294] (a) contacting an agent with an isolated protein encoded by an ORF of the present invention, or nucleic acid of the invention; and

[0295] (b) determining whether the agent binds to said protein or said nucleic acid.

[0296] In general, therefore, such methods for identifying compounds that bind to a polynucleotide of the invention can comprise contacting a compound with a polynucleotide of the invention for a time sufficient to form a polynucleotide/compound complex, and detecting the complex, so that if a polynucleotide/compound complex is detected, a compound that binds to a polynucleotide of the invention is identified.

[0297] Likewise, in general, therefore, such methods for identifying compounds that bind to a polypeptide of the invention can comprise contacting a compound with a polypeptide of the invention for a time sufficient to form a polypeptide/compound complex, and detecting the complex, so that if a polypeptide/compound complex is detected, a compound that binds to a polynucleotide of the invention is identified.

[0298] Methods for identifying compounds that bind to a polypeptide of the invention can also comprise contacting a compound with a polypeptide of the invention in a cell for a time sufficient to form a polypeptide/compound complex, wherein the complex drives expression of a receptor gene sequence in the cell, and detecting the complex by detecting reporter gene sequence expression, so that if a polypeptide/compound complex is detected, a compound that binds a polypeptide of the invention is identified.

[0299] Compounds identified via such methods can include compounds which modulate the activity of a polypeptide of the invention (that is, increase or decrease its activity, relative to activity observed in the absence of the compound). Alternatively, compounds identified via such methods can include compounds which modulate the expression of a polynucleotide of the invention (that is, increase or decrease expression relative to expression levels observed in the absence of the compound). Compounds, such as compounds identified via the methods of the invention, can be tested using standard assays well known to those of skill in the art for their ability to modulate activity/expression.

[0300] The agents screened in the above assay can be, but are not limited to, peptides, carbohydrates, vitamin derivatives, or other pharmaceutical agents. The agents can be selected and screened at random or rationally selected or designed using protein modeling techniques.

[0301] For random screening, agents such as peptides, carbohydrates, pharmaceutical agents and the like are selected at random and are assayed for their ability to bind to the protein encoded by the ORF of the present invention. Alternatively, agents may be rationally selected or designed. As used herein, an agent is said to be “rationally selected or designed” when the agent is chosen based on the configuration of the particular protein. For example, one skilled in the art can readily adapt currently available procedures to generate peptides, pharmaceutical agents and the like, capable of binding to a specific peptide sequence, in order to generate rationally designed antipeptide peptides, for example see Hurby et al., Application of Synthetic Peptides: Antisense Peptides,” In Synthetic Peptides, A User's Guide, W. H. Freeman, N.Y. (1992), pp. 289-307, and Kaspczak et al., Biochemistry 28:9230-8 (1989), or pharmaceutical agents, or the like.

[0302] In addition to the foregoing, one class of agents of the present invention, as broadly described, can be used to control gene expression through binding to one of the ORFs or EMFs of the present invention. As described above, such agents can be randomly screened or rationally designed/selected. Targeting the ORF or EMF allows a skilled artisan to design sequence specific or element specific agents, modulating the expression of either a single ORF or multiple ORFs which rely on the same EMF for expression control. One class of DNA binding agents are agents which contain base residues which hybridize or form a triple helix formation by binding to DNA or RNA. Such agents can be based on the classic phosphodiester, ribonucleic acid backbone, or can be a variety of sulfhydryl or polymeric derivatives which have base attachment capacity.

[0303] Agents suitable for use in these methods preferably contain 20 to 40 bases and are designed to be complementary to a region of the gene involved in transcription (triple helix—see Lee et al., Nucl. Acids Res. 6:3073 (1979); Cooney et al., Science 241:456 (1988); and Dervan et al., Science 251:1360 (1991)) or to the mRNA itself (antisense—Okano, J. Neurochem. 56:560 (1991); Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression, CRC Press, Boca Raton, FL (1988)). Triple helix-formation optimally results in a shut-off of RNA transcription from DNA, while antisense RNA hybridization blocks translation of an mRNA molecule into polypeptide. Both techniques have been demonstrated to be effective in model systems. Information contained in the sequences of the present invention is necessary for the design of an antisense or triple helix oligonucleotide and other DNA binding agents.

[0304] Agents which bind to a protein encoded by one of the ORFs of the present invention can be used as a diagnostic agent. Agents which bind to a protein encoded by one of the ORFs of the present invention can be formulated using known techniques to generate a pharmaceutical composition.

USE OF NUCLEIC ACIDS AS PROBES

[0305] Another aspect of the subject invention is to provide for polypeptide-specific nucleic acid hybridization probes capable of hybridizing with naturally occurring nucleotide sequences. The hybridization probes of the subject invention may be derived from any of the nucleotide sequences SEQ ID NOs: 1-91. Because the corresponding gene is only expressed in a limited number of tissues, a hybridization probe derived from of any of the nucleotide sequences SEQ ID NOs: 1-91 can be used as an indicator of the presence of RNA of cell type of such a tissue in a sample.

[0306] Any suitable hybridization technique can be employed, such as, for example, in situ hybridization. PCR as described in U.S. Pat. Nos. 4,683,195 and 4,965,188 provides additional uses for oligonucleotides based upon the nucleotide sequences. Such probes used in PCR may be of recombinant origin, may be chemically synthesized, or a mixture of both. The probe will comprise a discrete nucleotide sequence for the detection of identical sequences or a degenerate pool of possible sequences for identification of closely related genomic sequences.

[0307] Other means for producing specific hybridization probes for nucleic acids include the cloning of nucleic acid sequences into vectors for the production of mRNA probes. Such vectors are known in the art and are commercially available and may be used to synthesize RNA probes in vitro by means of the addition of the appropriate RNA polymerase as T7 or SP6 RNA polymerase and the appropriate radioactively labeled nucleotides. The nucleotide sequences may be used to construct hybridization probes for mapping their respective genomic sequences. The nucleotide sequence provided herein may be mapped to a chromosome or specific regions of a chromosome using well known genetic and/or chromosomal mapping techniques. These techniques include in situ hybridization, linkage analysis against known chromosomal markers, hybridization screening with libraries or flow-sorted chromosomal preparations specific to known chromosomes, and the like. The technique of fluorescent in situ hybridization of chromosome spreads has been described, among other places, in Verma et al (1988) Human Chromosomes: A Manual of Basic Techniques, Pergamon Press, New York N.Y.

[0308] Fluorescent in situ hybridization of chromosomal preparations and other physical chromosome mapping techniques may be correlated with additional genetic map data. Examples of genetic map data can be found in the 1994 Genome Issue of Science (265:1981f). Correlation between the location of a nucleic acid on a physical chromosomal map and a specific disease (or predisposition to a specific disease) may help delimit the region of DNA associated with that genetic disease. The nucleotide sequences of the subject invention maybe used to detect differences in gene sequences between normal, carrier or affected individuals.

PREPARATION OF SUPPORT BOUND OLIGONUCLEOTIDES

[0309] Oligonucleotides, i.e., small nucleic acid segments, may be readily prepared by, for example, directly synthesizing the oligonucleotide by chemical means, as is commonly practiced using an automated oligonucleotide synthesizer.

[0310] Support bound oligonucleotides may be prepared by any of the methods known to those of skill in the art using any suitable support such as glass, polystyrene or Teflon. One strategy is to precisely spot oligonucleotides synthesized by standard synthesizers. Immobilization can be achieved using passive adsorption (Inouye & Hondo, (1990) J. Clin. Microbiol. 28(6) 1469-72); using UV light (Nagata et al, 1985; Dahlen et al, 1987; Morrissey & Collins, (1989) Mol. Cell Probes 3(2) 189-207) or by covalent binding of base modified DNA (Keller et al., 1988; 1989); all references being specifically incorporated herein.

[0311] Another strategy that may be employed is the use of the strong biotin-streptavidin interaction as a linker. For example, Broude et al (1994) Proc. Natl. Acad. Sci. USA 91(8) 3072-6, describe the use of biotinylated probes, although these are duplex probes, that are immobilized on streptavidin-coated magnetic beads. Streptavidin-coated beads may be purchased from Dynal, Oslo. Of course, this same linking chemistry is applicable to coating any surface with streptavidin. Biotinylated probes may be purchased from various sources, such as, e.g., Operon Technologies (Alameda, Calif.).

[0312] Nunc Laboratories (Naperville, Ill.) is also selling suitable material that could be used. Nunc Laboratories have developed a method by which DNA can be covalently bound to the microwell surface termed Covalink NH. CovaLink NH is a polystyrene surface grafted with secondary amino groups (>NH) that serve as bridge-heads for further covalent coupling. CovaLink Modules may be purchased from Nunc Laboratories. DNA molecules may be bound to CovaLink exclusively at the 5′-end by a phosphoramidate bond, allowing immobilization of more than 1 pmol of DNA (Rasmussen et al., (1991) Anal. Biochem. 198(1) 138-42).

[0313] The use of CovaLink NH strips for covalent binding of DNA molecules at the 5′-end has been described (Rasmussen et al., (1991). In this technology, aphosphoramidate bond is employed (Chu et al., (1983) Nucleic Acids Res. 11(8) 6513-29). This is beneficial as immobilization using only a single covalent bond is preferred. The phosphoramidate bond joins the DNA to the CovaLink NH secondary amino groups that are positioned at the end of spacer arms covalently grafted onto the polystyrene surface through a 2 nm long spacer arm. To link an oligonucleotide to CovaLink NH via an phosphoramidate bond, the oligonucleotide terminus must have a 5′-end phosphate group. It is, perhaps, even possible for biotin to be covalently bound to CovaLink and then streptavidin used to bind the probes.

[0314] More specifically, the linkage method includes dissolving DNA in water (7.5 ng/ul) and denaturing for 10 min. at 95° C. and cooling on ice for 10 min. Ice-cold 0.1 M 1-methylimidazole, pH 7.0 (1-MeIn₇), is then added to a final concentration of 10 mM 1-MeIm₇. A ss DNA solution is then dispensed into CovaLink NH strips (75 ul/well) standing on ice.

[0315] Carbodiimide 0.2 M 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC), dissolved in 10 mnM 1-MeIm₇, is made fresh and 25 ul added per well. The strips are incubated for 5 hours at 50° C. After incubation the strips are washed using, e.g., Nunc-hlmuno Wash; first the wells are washed 3 times, then they are soaked with washing solution for 5 min., and finally they are washed 3 times (where in the washing solution is 0.4 N NaOH, 0.25% SDS heated to 50° C.).

[0316] It is contemplated that a firther suitable method for use with the present invention is that described in PCT Patent Application WO 90/03382 (Southern & Maskos), incorporated herein by reference. This method of preparing an oligonucleotide bound to a support involves attaching a nucleoside 3′-reagent through the phosphate group by a covalent phosphodiester link to aliphatic hydroxyl groups carried by the support. The oligonucleotide is then synthesized on the supported nucleoside and protecting groups removed from the synthetic oligonucleotide chain under standard conditions that do not cleave the oligonucleotide from the support. Suitable reagents include nucleoside phosphoramnidite and nucleoside hydrogen phosphorate.

[0317] An on-chip strategy for the preparation of DNA probe for the preparation of DNA probe arrays may be employed. For example, addressable laser-activated photodeprotection may be employed in the chemical synthesis of oligonucleotides directly on a glass surface, as described by Fodor et al (1991) Science 251(4995) 767-73, incorporated herein by reference. Probes may also be imnmobilized on nylon supports as described by Van Ness et al. (1991) Nucleic Acids Res. 19(12) 3345-50; or linked to Teflon using the method of Duncan & Cavalier (1988) Anal. Biochem. 169(1) 104-8; all references being specifically incorporated herein.

[0318] To link an oligonucleotide to a nylon support, as described by Van Ness et al. (1991), requires activation of the nylon surface via alkylation and selective activation of the 5′-amine of oligonucleotides with cyanuric chloride.

[0319] One particular way to prepare support bound oligonucleotides is to utilize the light-generated synthesis described by Pease et al., (1994) PNAS USA 91(11) 5022-6, incorporated herein by reference). These authors used current photolithographic techniques to generate arrays of immobilized oligonucleotide probes (DNA chips). These methods, in which light is used to direct the synthesis of oligonucleotide probes in high-density, miniaturized arrays, utilize photolabile 5′-protected N-acyl-deoxynucleoside phosphoramidites, surface linker chemistry and versatile combinatorial synthesis strategies. A matrix of 256 spatially defined oligonucleotide probes may be generated in this manner.

PREPARATION OF NUCLEIC ACID FRAGMENTS

[0320] The nucleic acids may be obtained from any appropriate source, such as cDNAs, genomic DNA, chromosomal DNA, microdissected chromosome bands, cosmid or YAC inserts, and RNA, including mRNA without any amplification steps. For example, Sambrook et al. (1989) describes three protocols for the isolation of high molecular weight DNA from mammalian cells (p. 9.14-9.23).

[0321] DNA fragments may be prepared as clones in M13, plasmid or lambda vectors and/or prepared directly from genomic DNA or cDNA by PCR or other amplification methods. Samples may be prepared or dispensed in multiwell plates. About 100-1000 ng of DNA samples may be prepared in 2-500 ml of final volume.

[0322] The nucleic acids would then be fragmented by any of the methods known to those of skill in the art including, for example, using restriction enzymes as described at 9.24-9.28 of Sambrook et al. (1989), shearing by ultrasound and NaOH treatment.

[0323] Low pressure shearing is also appropriate, as described by Schriefer et al. (1990) Nucleic Acids Res. 18(24) 7455-6, incorporated herein by reference). In this method, DNA samples are passed through a small French pressure cell at a variety of low to intermediate pressures. A lever device allows controlled application of low to intermediate pressures to the cell. The results of these studies indicate that low-pressure shearing is a useful alternative to sonic and enzymatic DNA fragmentation methods.

[0324] One particularly suitable way for fragmenting DNA is contemplated to be that using the two base recognition endonuclease, CviJI, described by Fitzgerald et al. (1992) Nucleic Acids Res. 20(14) 3753-62. These authors described an approach for the rapid fragmentation and fractionation of DNA into particular sizes that they contemplated to be suitable for shotgun cloning and sequencing.

[0325] The restriction endonuclease CviJI normally cleaves the recognition sequence PuGCPy between the G and C to leave blunt ends. Atypical reaction conditions, which alter the specificity of this enzyme (CviJI**), yield a quasi-random distribution of DNA fragments form the small molecule pUC19 (2688 base pairs). Fitzgerald et al. (1992) quantitatively evaluated the randomness of this fragmentation strategy, using a CviJI** digest of pUC19 that was size fractionated by a rapid gel filtration method and directly ligated, without end repair, to a lac Z minus M13 cloning vector. Sequence analysis of 76 clones showed that CviJI** restricts pyGCPy and PuGCPu, in addition to PuGCPy sites, and that new sequence data is accum-ulated at a rate consistent with random fragmentation.

[0326] As reported in the literature, advantages of this approach compared to sonication and agarose gel fractionation include: smaller amounts of DNA are required (0.2-0.5 ug instead of 2-5 ug); and fewer steps are involved (no preligation, end repair, chemical extraction, or agarose gel electrophoresis and elution are needed

[0327] Irrespective of the manner in which the nucleic acid fragments are obtained or prepared, it is important to denature the DNA to give single stranded pieces available for hybridization. This is achieved by incubating the DNA solution for 2-5 minutes at 80-90° C. The solution is then cooled quickly to 2° C. to prevent renaturation of the DNA fragments before they are contacted with the chip. Phosphate groups must also be removed from genomic DNA by methods known in the art.

PREPARATION OF DNA ARRAYS

[0328] Arrays may be prepared by spotting DNA samples on a support such as a nylon membrane. Spotting may be performed by using arrays of metal pins (the positions of which correspond to an array of wells in a microtiter plate) to repeated by transfer of about 20 nl of a DNA solution to a nylon membrane. By offset printing, a density of dots higher than the density of the wells is achieved. One to 25 dots may be accommodated in 1 mm², depending on the type of label used. By avoiding spotting in some preselected number of rows and columns, separate subsets (subarrays) may be formed. Samples in one subarray may be the same genomic segment of DNA (or the same gene) from different individuals, or may be different, overlapped genomic clones. Each of the subarrays may represent replica spotting of the same samples. In one example, a selected gene segment may be amplified from 64 patients. For each patient, the amplified gene segment may be in one 96-well plate (all 96 wells containing the same sample). A plate for each of the 64 patients is prepared. By using a 96-pin device, all samples may be spotted on one 8×12 cm membrane. Subarrays may contain 64 samples, one from each patient. Where the 96 subarrays are identical, the dot span may be 1 mm² and there may be a 1 mm space between subarrays.

[0329] Another approach is to use membranes or plates (available from NUNC, Naperville, Ill.) which may be partitioned by physical spacers e.g. a plastic grid molded over the membrane, the grid being similar to the sort of membrane applied to the bottom of multiwell plates, or hydrophobic strips. A fixed physical spacer is not preferred for imaging by exposure to flat phosphor-storage screens or x-ray films.

[0330] The present invention is illustrated in the following examples. Upon consideration of the present disclosure, one of skill in the art will appreciate that many other embodiments and variations may be made in the scope of the present invention. Accordingly, it is intended that the broader aspects of the present invention not be limited to the disclosure of the following examples. The present invention is not to be limited in scope by the exemplified embodiments which are intended as illustrations of single aspects of the invention, and compositions and methods which are functionally equivalent are within the scope of the invention. Indeed, numerous modifications and variations in the practice of the invention are expected to occur to those skilled in the art upon consideration of the present preferred embodiments. Consequently, the only limitations which should be placed upon the scope of the invention are those which appear in the appended claims.

[0331] All references cited within the body of the instant specification are hereby incorporated by reference in their entirety.

EXAMPLES Example 1 Novel Nucleic Acid Sequences Obtained From Various Libraries

[0332] A plurality of novel nucleic acids were obtained from cDNA libraries prepared from various human tissues and in some cases isolated from a genomic library derived from human chromosome using standard PCR, SBH sequence signature analysis and Sanger sequencing techniques. The inserts of the library were amplified with PCR using primers specific for the vector sequences which flank the inserts. Clones from cDNA libraries were spotted on nylon membrane filters and screened with oligonucleotide probes (e.g., 7-mers) to obtain signature sequences. The clones were clustered into groups of similar or identical sequences. Representative clones were selected for sequencing.

[0333] In some cases, the 5′ sequence of the amplified inserts was then deduced using a typical Sanger sequencing protocol. PCR products were purified and subjected to fluorescent dye terminator cycle sequencing. Single pass gel sequencing was done using a 377 Applied Biosystems (ABD sequencer to obtain the novel nucleic acid sequences. In some cases RACE Random Amplification of cDNA Ends) was performed to further extend the sequence in the 5′ direction.

Example 2 Novel Nucleic Acids

[0334] The novel nucleic acids of the present invention of the invention were assembled from sequences that were obtained from a cDNA library by methods described in Example 1 above, and in some cases sequences obtained from one or more public databases. The nucleic acids were assembled using an EST sequence as a seed. Then a recursive algorithm was used to extend the seed EST into an extended assemblage, by pulling additional sequences from different databases (i.e., Hyseq's database containing EST sequences, dbEST version 114, gb pri 114, and UniGene version 101) that belong to this assemblage. The algorithm terminated when there was no additional sequences from the above databases that would extend the assemblage. Inclusion of component sequences into the assemblage was based on a BLASTN hit to the extending assemblage with BLAST score greater than 300 and percent identity greater than 95%.

[0335] Using PIRAP (Univ. of Washington) or CAP4 (Paracel), a full length gene cDNA sequence and its corresponding protein sequence were generated from the assemblage. Any frame shifts and incorrect stop codons were corrected by hand editing. During editing, the sequence was checked using FASTY and/or BLAST against Genbank (i.e., dbEST version 118, gb pri 118, UniGene version 118, Genepet release 118). Other computer programs which may have been used in the editing process were phredPhrap and Consed (University of Washington) and ed-ready, ed-ext and gc-zip-2 (Hyseq, Inc.). The full-length nucleotide and amino acid sequences, including splice variants resulting from these procedures are shown in the Sequence Listing as SEQ ID NOS: 1-91.

[0336] Table 1 shows the various tissue sources of SEQ ID NO: 1-91.

[0337] The homology for SEQ ID NO: 1-91 were obtained by a BLASTP version 2.0al 19MP-WashU search against Genpept release 118, using BLAST algorithm. The results showed homologues for SEQ ID NO: 1-91 from Genpept. The homologues with identifiable functions for SEQ ID NO: 1-91 are shown in Table 2 below.

[0338] Using eMatrix software package (Stanford University, Stanford, Calif.) (Wu et al., J. Comp. Biol., Vol. 6 pp. 219-235 (1999) herein incorporated by reference), all the sequences were examined to determine whether they had identifiable signature regions. Table 3 shows the signature region found in the indicated polypeptide sequences, the description of the signature, the eMatrix p-value(s) and the position(s) of the signature within the polypeptide sequence.

[0339] Using the pFam software program (Sonnhammer et al., Nucleic Acids Res., Vol. 26(1) pp. 320-322 (1998) herein incorporated by reference) all the polypeptide sequences were examined for domains with homology to certain peptide domains. Table 4 shows the name of the domain found, the description, the p-value and the pFam score for the identified domain within the sequence.

[0340] The nucleotide sequence within the sequences that codes for signal peptide sequences and their cleavage sites can be determine from using Neural Network SignalP V1.1 program (from Center for Biological Sequence Analysis, The Technical University of Denmark). The process for identifying prokaryotic and eukaryotic signal peptides and their cleavage sites are also disclosed by Henrik Nielson, Jacob Engelbrecht, Soren Brunak, and Gunnar von Heijne in the publication “Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites” Protein Engineering, Vol. 10, no. 1, pp. 1-6 (1997), incorporated herein by reference. A maximum S score and a mean S score, as described in the Nielson et as reference, was obtained for the polypeptide sequences. Table 5 shows the position of the signal peptide in each of the polypeptides and the maximum score and mean score associated with that signal peptide. TABLE 1 HYSEQ TISSUE RNA LIBRARY ORIGIN SOURCE NAME SEQ ID NOS: adult brain GIBCO AB3001 11 17 27 33 37 39 53-54 68 70 88 91 adult brain GIBCO ABD003 11 20-21 24 29 33 38 42-43 45 50 52 54 56-57 62-65 70 72 76 82 84 88 90-91 adult brain Clontech ABR001 24 83 91 adult brain Clontech ABR006 11 91 adult brain Clontech ABR008 7 11-14 17-18 20-24 26-28 30 32-37 46 48 50-51 62 65 69- 70 74 76 80 86 90-91 adult brain BioChain ABR012 38 adult brain Invitrogen ABR013 37 adult brain Invitrogen ABR014 65 adult brain Invitrogen ABT004 7 11 18 23 28 32-33 37 39 52 65 68 91 cultured Strategene ADP001 4 13-14 23 38 43 72 preadipocytes adrenal gland Clontech ADR002 9 11 23 28 33-34 38 43 49-50 52 55 62 67 70 82 85 adult heart GIBCO AHR001 4 6-7 9 11-12 14 18 23-24 26 28-30 32-35 38 42-43 45 49 51 62-63 65 67 70-72 75-76 86 90 adult kidney GIBCO AKD001 3-4 6-7 9 11-12 14 16 18 21- 25 28-30 33-38 42-43 45 50- 52 54 57 61-67 70-72 75 80 85-90 adult kidney Invitrogen AKT002 3 9 28 30 33 38-39 53 61-62 72 75 85 90 adult lung GIBCO ALG001 7 18-19 24 28 34 38 43 46 50 64 72 lymph node Clontech ALN001 9 18 30 38 43 54 57 62 65 young liver GIBCO ALV001 4 7 9 11 19 23 30 33 49-50 63 75 adult liver Invitrogen ALV002 7 9 12 19 23 25-26 28 33-34 37 42 50 64-66 adult ovary Invitrogen AOV001 1 3-4 6-7 9-14 17-18 20-24 28-30 32-36 38-39 41 43 45 49-53 57-59 61-62 64-65 67 70-72 75-76 80 82 85-86 88- 89 adult placenta Clontech APL001 4 30 50 placenta Invitrogen APL002 36 45 51-52 89 adult spleen GIBCO ASP001 7 11-12 17-18 33 38 42 48 52 57 62 64 72-73 76 78 testis GIBCO ATS001 4 7 11-13 24 28 34-35 38 62 72 80 adult bladder Invitrogen BLD001 4 23 28 49 73 87 91 bone marrow Clontech BMD001 1 3 5 9-10 21-22 24 27-28 31 33 38-39 41 43 45 51-54 57 59-62 65 72-73 75-76 78 84 87 89-90 bone marrow Clontech BMD002 2-3 5 12 14 27 38 43 48 51 57 62 68-69 72-73 78 80 bone marrow Clontech BMD004 78 bone marrow Clontech BMD007 78 adult colon Invitrogen CLN001 33 36 52 88 Mixture of 16 Various CTL021 5 50 72 78 tissues- Vendors* mRNAs* adult cervix BioChain CVX001 1 4 9 12 14 20-21 27 29 33 42 45 52-53 60 62 67 72 75 81 84 endothelial Strategene EDT001 4 6-7 9-14 17-18 22-25 28-30 cells 33-34 36 38 42-43 45 47-48 50-51 53 57 59 62 65 67 70- 72 75 83 85 87 fetal brain Clontech FBR006 9 14 23 26 30 36 42-43 50 65 70 74 76-77 80 fetal brain Invitrogen FBT002 23 30 35 50-51 89 fetal heart Invitrogen FHR001 80 fetal kidney Clontech FKD001 13 33 38 42-43 50 72 fetal kidney Clontech FKD002 62 fetal kidney Invitrogen FKD007 13 fetal lung Clontech FLG001 3 35 57 62 78 fetal lung Invitrogen FLG003 4 57 fetal lung Clontech FLG004 62 fetal liver- Columbia FLS001 1-10 12-26 28 30-31 33 36-39 spleen University 42-52 57 59 61-67 69-72 75- 76 78-83 85-89 fetal liver- Columbia FLS002 3-4 8 10 12 15-16 18-21 23- spleen University 24 26-28 30-31 33 39 42-44 46 48 50-52 54 57 59 64 67 69-72 75-76 78 80 84 86-88 fetal liver- Columbia FLS003 5 84 86 spleen University fetal liver Invitrogen FLV001 5 7 15-16 19 26 28 30 33 37 48 52 69 85 89 fetal liver Clontech FLV004 28 48 fetal muscle Invitrogen FMS001 28 42 48 62 72 78 87 89 fetal muscle Invitrogen FMS002 1 62 89 fetal skin Invitrogen FSK001 1 3-7 9 13 15 20 30 36-37 42 48 52 62 70 72 82 85 87-89 fetal spleen BioChain FSP001 62 umbilical cord BioChain FUC001 4-5 10-13 15 24 29-30 33 38- 39 43 46 52 57 62 67 72 83 85-86 91 fetal brain GIBCO HFB001 6-9 11-14 17-18 20 24 27-28 30 32-34 36-37 42-43 49 51 56-57 59 62 67 72 74-75 77 87 91 macrophage Invitrogen HMP001 22 infant brain Columbia IB2002 5 7-8 11-12 20 23-24 26-27 University 32 37 39 49-50 52 55-56 62 65 70 74-76 86-88 91 infant brain Columbia IB2003 39 52 62 86-87 89-91 University infant brain Columbia IBM002 87 University infant brain Columbia IBS001 59 91 University lung, fibroblast Strategene LFB001 4 6 9 11 14 28 35 38 43 53 57 64 72 lung tumor Invitrogen LGT002 4 6 8-10 12 14 18 20-21 24 32-33 36 38 42-43 50-52 56- 57 61 63-65 72 75-76 79 85- 86 89 lymphocytes ATCC LPC001 11 14 22 35-36 50 59 62 86- 87 90 leukocyte GIBCO LUC001 6-12 14 18 24 27 30 33-36 38 42-43 45 52-53 57 59-62 64- 65 67 72-73 75-76 86 88-90 leukocyte Clontech LUC003 14 16 18 38 52 62 melanoma from Clontech MEL004 6 9 14 29 41 43 50-51 63 70 cell line 72 87 ATCC # CRL 1424 mammary Invitrogen MMG001 11-12 14-16 18-19 23-24 28 gland 30 33 36-38 42-43 46 50-52 59 62 64 72-73 86-89 induced neuron Strategene NTD001 7 11 13 32 42 57 62 82 cells neuronal cells Strategene NTU001 9 48 50 62 pituitary gland Clontech PIT004 6 53 82-83 prostate Clontech PRT001 11 24 29 50 55 61-62 65 70 rectum Invitrogen REC001 9 29-30 33 37 39 48 73 85-86 91 salivary gland Clontech SAL001 7 45 52-53 57 65 small intestine Clontech SIN001 4 39 61 72-73 75 90 skeletal muscle Clontech SKM001 9 71 spinal cord Clontech SPC001 1 3 15 64 71 adult spleen Clontech SPLc01 37 43 50 62 90 stomach Clontech STO001 49 51 89 thalamus Clontech THA002 9 23 43 55 89 91 thymus Clontech THM001 8 10 21 23 34 37-38 42 58 62 72 75 78 82 86-87 89 thymus Clontech THMc02 11-12 30 34 38 51 54 60 78 80 89 thyroid gland Clontech THR001 1 4 9 11 24 26 29-30 35 39 45-46 52-53 62 64-65 72 77 83 88 trachea Clontech TRC001 9 24 43 57 60 72 uterus Clontech UTR001 6 11 33 42 54 60 62-63 # 11) human thymus mRNA (Clontech), 12) human lymph node mRNA (Clontech), 13) human spinal cord mRNA (Clontech), 14) human thyroid mRNA (Clontech), 15) human esophagus mRNA (BioChain), 16) human conceptional umbilical cord mRNA (BioChain).

[0341] TABLE 2 CORRESPONDING SEQ ID NO. IN SMITH- SEQ ID U.S.S.N ACCESSION WATERMAN NO: 09/552,929 NUMBER DESCRIPTION SCORE % IDENTITY 1 151 U11031 Rattus norvegicus 213 25 BIG-1 protein 2 608 AF156961 Homo sapiens gag 1762 91 3 649 S79410 Mus musculus 94 43 nuclear localization signal binding protein 4 940 X01802 Drosophila 74 35 melanogaster put. vitelline reading frame 5 954 V00488 Homo sapiens alpha 733 100 globin 6 990 X72964 Homo sapiens 856 100 caltractin 7 1009 AL034393 Caenorhabditis 525 44 1010 elegans Y18D10A.3 8 1030 AF010144 Homo sapiens 182 69 neuronal thread protein AD7c-NTP 9 1033 X60036 Homo sapiens 1897 100 phosphate carrier protein 10 1036 X54942 Homo sapiens Cks1 439 100 1037 protein homologue 11 1051 X56468 Homo sapiens 14.3.3 1246 100 protein 12 1070 X78136 Homo sapiens hnRNP- 1850 99 1071 E2 1072 1073 1074 13 1091 AF129332 Homo sapiens MUM2 767 100 14 1092 AB002282 Homo sapiens 749 100 1093 hMBF1alpha 15 1108 X07868 Homo sapiens 1.8 kb 451 98 1109 mRNA (AA 1-84) 1110 16 1136 K03473 Homo sapiens 380 100 1137 metallothionein I-F 1138 1139 17 1181 AF161472 Homo sapiens 496 78 HSPC123 18 1197 X98253 Homo sapiens ZNF183 1860 100 1198 19 1220 M36803 Homo sapiens 2603 100 1221 hemopexin 20 1247 M32015 Mus musculus 131 26 lysosomal membrane glycoprotein-type A precursor 21 1268 AF019980 Dictyostelium 173 24 1269 discoideum ZipA 22 1328 AF198092 Mus musculus RP42 1359 99 1329 23 1330 J02888 Homo sapiens 513 95 1331 quinone 1332 oxidoreductase 24 1360 AB007141 Mus musculus AZ2 1700 81 1361 1362 25 1390 AF129756 Homo sapiens Apo M 1016 100 26 1393 U87318 Xenopus laevis 1161 55 1394 NaDC-2 1395 1396 1397 1398 1399 1400 27 1412 U63111 Rattus norvegicus 116 26 1413 dentin 1414 phosphoprotein precursor 28 1416 X12517 Homo sapiens C 918 100 protein (AA 1-159) 29 1435 X70476 Homo sapiens 4751 100 1436 subunit of coatomer complex 30 1437 AJ242910 Homo sapiens N- 1242 98 1438 Acetylglucosamine 1439 kinase 1440 1441 1442 1443 1444 1445 31 1474 X08055 Homo sapiens 314 100 1475 preglycophorin B 1476 32 1508 AF143235 Homo sapiens 1132 99 apoptosis related protein APR-1 33 1517 AF197952 Homo sapiens 345 94 1518 thioredoxin 1519 peroxidase PMP20 34 1528 AF081281 Homo sapiens 275 34 1529 lysophospholipase 35 1543 AF151036 Homo sapiens 808 100 1544 HSPC202 36 1596 AL008583 Homo sapiens 565 100 dJ327J16.1 (dynein, axonemal, light polypeptide 4) 37 1609 L76200 Homo sapiens 198 100 1610 guanylate kinase 1611 38 1619 L38941 Homo sapiens 582 97 1620 ribosomal protein L34 39 1644 U41548 Caenorhabditis 453 42 elegans weak similarity to hemolysins 40 1698 U05255 Homo sapiens 245 97 1699 glycophorin HeP2 1700 41 1714 X51699 Homo sapiens bone 526 100 Gla precursor (100 AA) 42 1743 X83218 Homo sapiens ATP 1032 99 1744 synthase, oligomycin sensitivity conferring protein 43 1834 X63527 Homo sapiens 990 100 1835 ribosomal protein L19 44 1847 L24521 Homo sapiens 94 53 transformation- related protein 45 1887 AF149414 Arabidopsis 299 37 1888 thaliana contains 1889 similarity to Pfam 1890 family PF00145 (C-S 1891 cytosine-specific 1892 DNA methylase); score=10.4. E=0.051, N=1 46 1981 X99920 Homo sapiens S100 186 38 calcium-binding protein A13 (S100A13) 47 2033 X92896 Homo sapiens ITBA2 568 99 2034 48 2063 U47924 Homo sapiens C8 1400 100 2064 49 2119 AF243495 Homo sapiens 2530 99 2120 hepatocellular 2121 carcinoma- 2122 associated antigen 67 50 2138 U37429 Caenorhabditis 314 40 2139 elegans similar to 2140 C18F10.5 51 2141 X12791 Homo sapiens l9kD 742 100 2142 SRP-protein (AA 1 - 2143 144) 52 2189 AJ006973 Homo sapiens TOM1 2515 100 2190 2191 2192 53 2194 AF067622 Caenorhabditis 200 49 2195 elegans Contains 2196 similarity to Pfam domain: PF00628 (PHD), Score=36.7, E-value=1.7e-07, N=2 54 2200 X84194 Homo sapiens 200 100 acylphosphatase 55 2247 AF119851 Homo sapiens 180 55 2248 PR01722 2249 2250 2251 2252 2253 56 2255 AF221520 Homo sapiens basic 1772 99 helix-loop-helix protein class B 1 57 2288 U66372 Bos taurus 313 98 2289 ribosomal protein 2290 S29 58 2311 AF000944 Rattus norvegicus 269 77 2312 TFIIA small subunit 59 2324 AL161746 Arabidopsis 379 49 2325 thaliana putative protein 60 2334 AB007774 Homo sapiens 508 100 cystatin A 61 2340 Y15909 Homo sapiens DIA- 5638 99 2341 156 protein 62 2353 AB015610 Chlorocebus 660 99 2354 aethiops ribosomal 2355 protein S4X 63 2373 X95384 Homo sapiens 14.5 675 100 2374 kDa translational inhibitor protein, p14.5 64 2401 M92449 Homo sapiens 1285 98 2402 putative 65 2403 U93868 Homo sapiens RNA 470 47 2404 polymerase III 2405 subunit 2406 66 2424 X76717 Homo sapiens MT-11 382 100 2425 protein 67 2756 AF212862 Homo sapiens 1774 100 2757 membrane interacting protein of RGS16 68 2811 Z97209 Schizosaccharomyces 299 35 pombe putative fatty acid hydroxylase 69 2844 AF082516 Homo sapiens I-1 110 32 receptor candidate protein 70 2854 AF174593 Homo sapiens F-box 2355 100 2855 protein Fb17 2856 2857 2858 2859 2860 71 2861 AB038021 Homo sapiens CLST 516 100 2862 11240 protein 2863 72 2882 X77953 Rattus norvegicus 671 100 2883 ribosomal protein 2884 S15a 73 2899 U24080 Homo sapiens 624 93 2900 immunoglobulin 2901 heavy chain VH3 2902 2903 74 2938 AF023268 Homo sapiens cotel 470 41 75 2974 AF077034 Homo sapiens 365 92 2975 HSPC010 2976 2977 76 2980 AF116618 Homo sapiens 626 51 2981 PR01038 2982 2983 2984 2985 2986 77 3000 AL080239 Homo sapiens 1704 50 3001 bG256022.1 (similar to IGFALS (insulin- like growth factor binding protein, acid labile subunit)) 78 3045 X13621 Homo sapiens HNP-3 495 100 defensin (AA 1- 94) 79 3083 X85373 Homo sapiens Sm 387 100 protein G 80 3111 AF160904 Drosophila 225 30 melanogaster BcDNA.HL05936 81 3138 AF084256 Homo sapiens beta 129 62 glucuronidase isoform d 82 3160 AL035461 Homo sapiens 3096 100 3161 dJ967N21.5 (novel MCM2/3/5 family member) 83 3382 AF006129 Acipenser 66 26 schrenckii cytochrome b 84 3503 AF074016 Homo sapiens 334 37 nonsense-mediated mRNA decay trans- acting factor 85 3934 AF151076 Homo sapiens 591 94 3935 HSPC242 3936 3937 86 4214 AJ277841 Homo sapiens ELG 1744 100 4215 protein 4216 87 4341 AJ250092 Bordetella 84 36 bronchiseptica pertactin (P.68) 88 4385 Z69381 Saccharomyces 182 29 cerevisiae N1106 89 4874 K03204 Homo sapiens 182 29 salivary proline- rich protein precursor 90 5591 AF117649 Drosophila 766 39 melanogaster Adrift 91 5597 AJ250425 Rattus norvegicus 1530 63 5598 Collybistin I 5599 5600 5601 5602

[0342] TABLE 3 SEQ ID NO: ACCESSION NO. DESCRIPTION RESULTS* 1 PR00761 BINDIN PRECURSOR PR00761E 14.32 4.500e-10 460-479 SIGNATURE PR00761E 14.32 7.253e-09 459-478 3 PR00676 MASPIN SIGNATURE PR00676G 9.32 9.460e-06 44-57 5 PR00611 ERYTHROCRUORIN FAMILY PR00611A 15.91 5.829e-09 74-97 SIGNATURE 6 PR00450 RECOVERIN FAMILY PR00450C 12.22 3.520e-10 62-84 SIGNATURE 8 PR00513 5-HYDROXYTRYPTAMINE 1B PR00513D 11.06 9.743e-07 47-65 RECEPTOR SIGNATURE 9 BL00439 Acyltransferases BL00439A 9.40 8.279e-09 341-358 ChoActase/COT/CPT family proteins. 10 PR00919 THERMOPHILIC PR00919G 12.82 5.684e-09 39-62 METALLOPROTEASE (M29) SIGNATURE 11 BL00796 14-3-3 proteins. BL00796C 17.44 1.000e-40 97-147 BL00796D 17.39 1.000e-40 148-194 BL00796E 14.15 1.000e-40 196-232 BL00796B 10.67 4.484e-37 35-68 BL00796A 10.52 3.571e-25 3-30 12 PR00332 HISTIDINE TRIAD FAMILY PR00332B 13.62 5.135e-09 279-298 SIGNATURE 13 PR00517 5-HYDROXYTRYPTAMINE 2C PR00517G 16.45 9.919e-06 20-36 RECEPTOR SIGNATURE 14 BL00665 Dihydrodipicolinate BL00665E 20.33 9.407e-06 35-61 synthetase proteins. 15 PR00733 GLYCOSYL HYDROLASE PR00733G 15.54 9.550e-06 34-55 FAMILY 6 SIGNATURE 16 PR00873 ECHINOIDEA (SEA PR00873D 8.43 9.315e-09 9-28 URCHIN) METALLOTHIONEIN SIGNATURE 18 BL00518 Zinc finger, C3HC4 BL00518 12.23 1.333e-09 277-286 type (RING finger), proteins. 19 PR00334 HMW KININOGEN PR00334B 8.69 7.857e-09 233-257 SIGNATURE 20 BL00310 Lysosome-associated BL00310A 14.05 2.102e-11 56-71 membrane glycoproteins duplicated domain proteins. 21 PR00514 5-HYDROXYTRYPTAMINE 1D PR00514D 8.30 6.400e-06 65-79 RECEPTOR SIGNATURE 22 PR00181 MALTOSE BINDING PR00181D 9.62 1.000e-05 134-154 PROTEIN SIGNATURE 23 DM00604 2 SHIGA/RICIN DM00604A 6.27 8.338e-06 105-115 RIBOSOMAL INACTIVATING TOXINS. 24 PD02474 SYNTHASE SMALL SUBUNIT PD02474B 21.08 9.752e-06 54-93 ACETOLACT. 25 PR00652 5-HYDROXYTRYPTAMINE 7 PR00652A 8.92 2.440e-06 109-130 RECEPTOR SIGNATURE 26 BL01271 Sodium: sulfate BL01271D 25.26 5.154e-38 480-535 symporter family BL01271B 12.02 6.400e-24 208-233 proteins. BL01271A 8.06 7.955e-23 132-152 BL01271C 13.62 7.429e-20 407-429 27 PR00519 5-HYDROXYTRYPTAMINE 5B PR00519B 9.99 7.000e-07 191-208 RECEPTOR SIGNATURE 28 DM00215 PROLINE-RICH PROTEIN 3. DM00215 19.43 3.898e-09 78-111 29 BL00678 Trp-Asp (WD) repeat BL00678 9.67 9.100e-12 246-257 proteins proteins. BL00678 9.67 4.600e-10 160-171 BL00678 9.67 4.789e-09 204-215 BL00678 9.67 1.000e-08 116-127 30 PR00245 OLFACTORY RECEPTOR PR00245A 18.03 7.848e-17 221-243 SIGNATURE PR00245D 10.47 8.500e-15 253-265 PR00245E 12.40 5.345e-09 270-285 31 BL00312 Glycophorin A BL00312B 9.22 7.517e-32 37-66 proteins. 32 PR00003 4-DISULPHIDE CORE PR00003B 7.64 2.200e-06 186-194 SIGNATURE 33 DM01803 1 HERPESVIRUS DM01803I 15.63 5.408e-06 83-119 GLYCOPROTEIN H. 34 PF00756 Putative esterase. PF00756C 14.12 7.692e-10 119-149 35 BL00366 Uricase proteins. BL00366E 21.95 1.000e-05 115-151 36 BL01239 Dynein light chain BL01239 16.10 1.099e-13 32-86 type 1 proteins. 37 BL00674 AAA-protein family BL100674B 4.46 9.392e-09 4-26 proteins. 38 BL01145 Ribosomal protein L34e BL01145A 13.73 1.000e-40 3-45 proteins. BL01145B 14.65 2.636e-20 88-111 40 BL00022 EGF-like domain BL00022B 7.54 1.000e-05 33-40 proteins. 41 PR00002 BONE MATRIX GLA DOMAIN PR00002A 11.56 7.000e-20 68-85 SIGNATURE PR00002B 8.36 4.316e-13 87-98 42 PR00125 ATP SYNTHASE DELTA PR00125E 13.56 9.250e-16 184-203 SUBUNIT SIGNATURE PR00125A 16.03 8.364e-15 37-57 PR00125D 11.00 5.345e-11 169-185 PR00125B 12.78 8.125e-10 106-118 43 BL00526 Ribosomal protein L19e BL00526A 19.50 1.000e-40 4-47 proteins. BL00526B 26.53 1.000e-40 53-100 BL00526C 20.60 1.000e-40 100-143 44 BL00366 Uricase proteins. BL00366D 21.56 9.928e-06 3-48 45 DM00604 2 SHIGA/RICIN DM00604D 13.26 8.125e-06 61-71 RIBOSOMAL INACTIVATING TOXINS. 46 PR00701 60KD INNER MEMBRANE PR00701G 13.83 9.056e-06 66-90 PROTEIN SIGNATURE 47 DM01554 1 THYROLIBERIN DM01554D 11.31 8.755e-06 54-68 PRECURSOR. 49 PR00683 SPECTRIN PLECKSTRIN PR00683B 16.62 5.558e-09 250-272 HOMOLOGY DOMAIN SIGNATURE 50 BL00785 5′-nucleotidase BL00785B 10.65 8.522e-06 5-19 proteins. 51 PR00925 NONHISTONE CHROMOSOMAL PR00925C 5.57 1.000e-05 133-144 PROTEIN HMG17 FAMILY SIGNATURE 52 DM01242 3 THREONINE-TRNA DM01242B 23.57 1.288e-06 63-112 LIGASE. 53 PF00628 PHD-finger. PF00628 15.84 5.125e-11 37-52 54 PR00112 ACYLPHOSPHATASE PR00112C 18.81 5.725e-23 4-25 SIGNATURE 55 PR00682 ISOPENICILLIN N PR00682A 11.84 9.314e-06 30-48 SYNTHASE SIGNATURE 56 PR00456 RIBOSOMAL PROTEIN P2 PR00456E 3.06 8.747e-09 449-464 SIGNATURE 58 PF00604 Influenza RNA- PF00604E 9.09 1.720e-06 9-64 dependant RNA polymerase subunit PB2. 59 BL00064 L-lactate BL00064F 25.14 7.720e-09 121-166 dehydrogenase proteins. 60 PR00295 STEFIN A SIGNATURE PR00295A 11.44 3.912e-21 4-24 PR00295C 10.99 8.297e-20 47-67 PR00295B 13.17 1.628e-19 27-47 PR00295D 10.30 3.919e-17 80-98 61 DM00215 PROLINE-RICH PROTEIN 3. DM00215 19.43 8.630e-13 572-605 DM00215 19.43 8.875e-12 571-604 DM00215 19.43 3.471e-11 560-593 DM00215 19.43 7.882e-11 583-616 DM00215 19.43 5.982e-10 558-591 DM00215 19.43 8.554e-10 547-580 DM00215 19.43 3.441e-09 588-621 DM00215 19.43 4.051e-09 559-592 DM00215 19.43 8.932e-09 556-589 DM00215 19.43 9.847e-09 574-607 62 BL00528 Ribosomal protein S4e BL00528B 24.75 1.000e-40 47-101 proteins. BL00528A 16.12 5.000e-36 3-36 63 BL01094 Hypothetical BL01094B 20.31 1.000e-40 49-99 YER057c/yjjV family BL01094A 16.79 7.188e-35 9-42 proteins. BL01094C 18.20 5.821e-28 99-129 64 PR00519 5-HYDROXYTRYPTAMINE 5B PR00519E 3.58 5.046e-07 300-315 RECEPTOR SIGNATURE 65 BL00412 Neuromodulin (GAP-43) BL00412D 16.54 6.786e-12 140-191 proteins. BL00412D 16.54 4.228e-10 146-197 BL00412D 16.54 6.576e-10 139-190 BL00412D 16.54 3.480e-09 138-189 BL00412D 16.54 6.143e-09 145-196 BL00412D 16.54 8.255e-09 132-183 66 PR00876 NEMATODE PR00876D 5.77 5.431e-11 15-28 METALLOTHIONEIN PR00876A 6.60 5.629e-09 14-27 SIGNATURE 67 PD01922 PROTEIN PD01922B 21.83 7.000e-22 78-114 PHOSPHODIESTERASE HYDROL. 68 DM01930 2 kw FINGER SMCX SMCY DM01930D 12.11 6.918e-07 172-183 YDR096W. 69 PR00651 5-HYDROXYTRYPTAMINE 2B PR00651C 8.81 9.681e-07 51-70 RECEPTOR SIGNATURE 70 DM01688 2 POLY-IG RECEPTOR. DM01688J 14.69 7.769e-06 310-347 71 PR00352 3FE-4S FERREDOXIN PR00352C 12.19 2.227e-06 64-77 SIGNATURE 72 BL00053 Ribosomal protein S8 BL00053C 16.71 5.500e-26 98-131 proteins. BL00053B 14.56 4.789e-14 58-76 BL00053A 8.83 5.320e-12 5-18 73 DM00031 IMMUNOGLOBULIN V DM00031A 16.80 1.000e-40 20-68 REGION. DM00031B 15.41 1.000e-40 84-118 74 PR00806 VINCULIN SIGNATURE PR00806A 6.63 6.055e-09 142-153 75 DM00547 1 kw CHROMO DM00547A 12.38 3.149e-06 355-367 BROMODOMAIN SHADOW GLOBAL. 76 PR00109 TYROSINE KINASE PR00109B 12.27 5.359e-09 148-167 CATALYTIC DOMAIN SIGNATURE 77 PR00019 LEUCINE-RICH REPEAT PR00019B 11.36 8.650e-10 456-470 SIGNATURE PR00019A 11.19 4.000e-09 202-216 PR00019A 11.19 9.333e-09 459-473 78 BL00269 Mammalian defensins BL00269C 16.52 6.786e-26 352-381 proteins. BL00269A 8.53 2.607e-20 287-307 BL00269B 19.17 2.800e-18 148-177 BL00269B 19.17 5.500e-17 314-343 BL00269A 8.53 2.731e-14 122-142 79 PD01861 PROTEIN NUCLEAR PD01861A 14.06 1.265e-19 24-48 RIBONUCLEOPROTEIN PD01861B 8.80 2.241e-11 58-71 SMALL MRNA RNA. 81 BL00305 11-S plant seed BL00305A 15.12 5.576e-06 5-19 storage proteins. 82 BL00847 MCM family proteins. BL00847F 32.02 7.070e-30 471-526 BL00847D 15.16 6.647e-21 357-398 BL00847E 17.27 3.250e-20 414-460 BL00847H 9.24 2.317e-15 620-638 BL00847E 17.27 4.411e-11 413-459 BL00847G 12.77 2.469e-09 591-611 BL00847A 25.87 1.000e-08 199-233 86 BL00422 Granins proteins. BL00422C 16.18 9.824e-09 65-93 87 BL00415 Synapsins proteins. BL00415N 4.29 4.153e-09 37-81 91 PF00564 Octicosapeptide repeat PF00564B 24.74 6.651e-09 399-450 proteins.

[0343] TABLE 4 SEQ ID pFAM NO: pFAM NAME DESCRIPTION p-value SCORE 1 ig Immunoglobulin domain 2.8e-22 76.9 2 gag_MA Matrix protein (MA), 0.0015 −20.2 p15 5 globin Globin 4.6e-57 203.0 6 efhand EF hand 3.5e-31 117.0 9 mito_carr Mitochondrial carrier  1.5e-112 387.3 proteins 10 CKS Cyclin-dependent 8.5e-50 178.9 kinase regulatory subunit 11 14-3-3 14-3-3 proteins  1.1e-147 504.0 12 KH-domain KH domain 2.9e-36 122.4 14 HTH_3 Helix-turn-helix 2.5e-06 34.5 16 metalthio Metallothionein 1.2e-24 95.4 18 zf-C3HC4 Zinc finger, C3HC4 0.0045 14.2 type (RING finger) 19 hemopexin Hemopexin 2.4e-58 207.3 26 Na_sulph_symp Sodium: sulfate 0.0014 −246.8 symporter transmembrane 29 WD40 WD domain, G-beta 7.5e-54 192.3 repeat 30 7tm_1 7 transmembrane 4.5e-10 34.2 receptor (rhodopsin family) 31 Glycophorin_A Glycophorin A 0.00015 7.6 32 MAGE MAGE family 0.05 −101.0 36 Dynein_light Dynein light chain 1.3e-12 55.3 type 1 38 Ribosomal_L34e Ribosomal protein L34e   1e-65 231.7 39 cNMP_binding Cyclic nucleotide- 0.05 10.1 binding domain 41 gla Vitamin K-dependent 2.2e-15 64.6 carboxylation/gamma- carb 42 OSCP ATP synthase delta 2.7e-75 257.7 (OSCP) subunit 43 Ribosomal_L19e Ribosomal protein L19e  3.6e-104 359.5 46 S_100 S-100/ICaBP type 2.9e-08 40.9 calcium binding domain 49 PH PH domain 8.1e-17 65.1 51 SRP19 SRP19 protein 1.2e-25 98.7 52 VHS VHS domain 9.6e-71 248.4 54 Acylphosphatase Acylphosphatase 0.0027 5.0 56 HLH Helix-loop-helix DNA-   5e-05 30.1 binding domain 57 Ribosomal_S14 Ribosomal protein 7.5e-20 68.3 S14p/S29e 59 HIT HIT family 0.0001 4.1 60 cystatin Cystatin domain 1.2e-24 95.4 62 Ribosomal_S4e Ribosomal family S4e 4.6e-08 40.2 63 UPF0076 Domain of unknown 9.9e-68 238.4 function 66 metalthio Metallothionein 2.2e-23 91.1 69 PX PX domain 1.7e-09 45.0 70 F-box F-box domain. 0.065 19.8 72 Ribosomal_S8 Ribosomal protein S8   6e-58 192.1 73 ig Immunoglobulin domain 3.1e-12 44.5 76 pkinase Eukaryotic protein 1.1e-30 114.5 kinase domain 77 LRRCT Leucine rich repeat   9e-17 69.1 C-terminal domain 78 defensins Mammalian defensin 2.8e-14 57.7 79 Sm Sm protein 1.1e-24 95.5 82 MCM MCM2/3/5 family 8.3e-99 341.7 90 FtsJ FtsJ cell division 0.00037 −37.0 protein 91 SH3 SH3 domain 7.9e-11 49.4

[0344] TABLE 5 POSITION OF SIGNAL IN maxS meanS AMINO ACID (MAXIMUM (MEAN SEQ ID NO: SEQUENCE SCORE) SCORE) 1 1-30 0.928 0.784 7 1-24 0.962 0.730 8 1-33 0.931 0.710 19 1-31 0.987 0.804 25 1-22 0.960 0.789 26 1-30 0.986 0.858 40 1-16 0.991 0.955 41 1-23 0.989 0.917 50 1-33 0.972 0.922 64 1-28 0.962 0.806 67 1-31 0.987 0.852 73 1-19 0.956 0.866 74 1-18 0.966 0.843

[0345]

1 91 1 2584 DNA Homo sapiens CDS (365)..(1984) 1 aaagccctcc tcccgggcca aggtagagga agttgggctc ccgcctggct gggaggcggg 60 agggatcccg ctcctgttgt tttccgccgg caggagtagg ctggcgggcg cagggggcgg 120 ggtgcgccct ccctccccgg ccagggcgct cgggagcggg gacccgagcc tgcagccgag 180 ctccgctgcc ggccctggac actcggctca gccaagcatc cttcctgggg gccgaggaag 240 tggggccact ctgccgttcc gaggacctgg gaggagccct cggtaccccg ggccccgggg 300 ccctggggca cacacgtcca gcccagcccg agcctgcgtt tcctgagccg ggatctgggg 360 cgag atg gcc gca ggc ggc agt gcg ccc gag ccc cgc gtc ctc gtc tgc 409 Met Ala Ala Gly Gly Ser Ala Pro Glu Pro Arg Val Leu Val Cys 1 5 10 15 ctc ggg gcg ctc ctg gcc ggc tgg gtc acc gta gga ttg gag gct gtt 457 Leu Gly Ala Leu Leu Ala Gly Trp Val Thr Val Gly Leu Glu Ala Val 20 25 30 gtc att tgg aga agt tat gag aat gtt act ctg cac tgt ggc aac atc 505 Val Ile Trp Arg Ser Tyr Glu Asn Val Thr Leu His Cys Gly Asn Ile 35 40 45 tcg gga ctg agg ggc cag gtg acc tgg tac cgg aac aac tcg gag cct 553 Ser Gly Leu Arg Gly Gln Val Thr Trp Tyr Arg Asn Asn Ser Glu Pro 50 55 60 gtc ttc ctt ctc tcg tcc aac tct agc ctc cgg cca gct gag cct cgc 601 Val Phe Leu Leu Ser Ser Asn Ser Ser Leu Arg Pro Ala Glu Pro Arg 65 70 75 ttc tct cta gtg gat gcc acc tcc ctg cac att gaa tcg ctg agc ctg 649 Phe Ser Leu Val Asp Ala Thr Ser Leu His Ile Glu Ser Leu Ser Leu 80 85 90 95 gga gat gag gga atc tac acc tgc cag gag atc ctg aat gtg act cag 697 Gly Asp Glu Gly Ile Tyr Thr Cys Gln Glu Ile Leu Asn Val Thr Gln 100 105 110 tgg ttc caa gtg tgg ctg cag gtg gcc agc ggc ccc tat cag att gag 745 Trp Phe Gln Val Trp Leu Gln Val Ala Ser Gly Pro Tyr Gln Ile Glu 115 120 125 gtc cac atc gtg gcc acc ggc aca ctc ccc aac ggc acc ctc tac gca 793 Val His Ile Val Ala Thr Gly Thr Leu Pro Asn Gly Thr Leu Tyr Ala 130 135 140 gcc agg ggc tcc cag gtg gac ttc agc tgc aac agc agc tcc agg cca 841 Ala Arg Gly Ser Gln Val Asp Phe Ser Cys Asn Ser Ser Ser Arg Pro 145 150 155 cca ccc gtg gtt gaa tgg tgg ttc cag gcc ctg aat tcc agc agc gag 889 Pro Pro Val Val Glu Trp Trp Phe Gln Ala Leu Asn Ser Ser Ser Glu 160 165 170 175 tcc ttt ggc cac aac ctg aca gtc aac ttt ttc tca ctg tta ctg ata 937 Ser Phe Gly His Asn Leu Thr Val Asn Phe Phe Ser Leu Leu Leu Ile 180 185 190 tcg cca aac ctc caa ggg aac tac acc tgt tta gcc ttg aat cag ctc 985 Ser Pro Asn Leu Gln Gly Asn Tyr Thr Cys Leu Ala Leu Asn Gln Leu 195 200 205 agc aag aga cat cga aag gtg acc acc gag ctc ctg gtc tac tat ccc 1033 Ser Lys Arg His Arg Lys Val Thr Thr Glu Leu Leu Val Tyr Tyr Pro 210 215 220 cct cca tca gct ccc cag tgc tgg gca cag atg gca tca gga tcg ttc 1081 Pro Pro Ser Ala Pro Gln Cys Trp Ala Gln Met Ala Ser Gly Ser Phe 225 230 235 atg ttg cag ctt acc tgt cgc tgg gat ggg gga tac cct gac cct gac 1129 Met Leu Gln Leu Thr Cys Arg Trp Asp Gly Gly Tyr Pro Asp Pro Asp 240 245 250 255 ttc ctg tgg ata gaa gag cca gga ggt gta atc gtg ggg aag tca aag 1177 Phe Leu Trp Ile Glu Glu Pro Gly Gly Val Ile Val Gly Lys Ser Lys 260 265 270 ctg ggg gtg gaa atg ctg agc gag tcc cag ctg tcg gat ggc aag aag 1225 Leu Gly Val Glu Met Leu Ser Glu Ser Gln Leu Ser Asp Gly Lys Lys 275 280 285 ttc aag tgt gtt aca agc cac ata gtt ggg cca gag tcg ggc gcc agc 1273 Phe Lys Cys Val Thr Ser His Ile Val Gly Pro Glu Ser Gly Ala Ser 290 295 300 tgc atg gtg cag atc agg ggt ccc tcc ctt ctc tct gag ccc atg aag 1321 Cys Met Val Gln Ile Arg Gly Pro Ser Leu Leu Ser Glu Pro Met Lys 305 310 315 act tgc ttc act ggg ggc aat gtg acg ctt aca tgc cag gtg tct ggg 1369 Thr Cys Phe Thr Gly Gly Asn Val Thr Leu Thr Cys Gln Val Ser Gly 320 325 330 335 gcc tac ccc cct gcc aag atc ctg tgg ctg agg aac ctt acc cag ccc 1417 Ala Tyr Pro Pro Ala Lys Ile Leu Trp Leu Arg Asn Leu Thr Gln Pro 340 345 350 gag gtg atc atc cag cct agc agc cgc cat ctc att acc cag gat ggc 1465 Glu Val Ile Ile Gln Pro Ser Ser Arg His Leu Ile Thr Gln Asp Gly 355 360 365 cag aac tcc acc ctc act atc cac aac tgc tcc cag gac ctg gat gag 1513 Gln Asn Ser Thr Leu Thr Ile His Asn Cys Ser Gln Asp Leu Asp Glu 370 375 380 ggc tac tac atc tgc cga gct gac agc cct gta ggg gtg agg gag atg 1561 Gly Tyr Tyr Ile Cys Arg Ala Asp Ser Pro Val Gly Val Arg Glu Met 385 390 395 gaa atc tgg ctg agt gtg aaa gaa cct tta aat atc ggg ggg att gtg 1609 Glu Ile Trp Leu Ser Val Lys Glu Pro Leu Asn Ile Gly Gly Ile Val 400 405 410 415 gga acc att gtg agc ctc ctt ctg ctg gga ctg gcc att atc tca ggg 1657 Gly Thr Ile Val Ser Leu Leu Leu Leu Gly Leu Ala Ile Ile Ser Gly 420 425 430 ctt ctg ttg cat tat agc cct gtg ttc tgc tgg aaa gga aac act tcc 1705 Leu Leu Leu His Tyr Ser Pro Val Phe Cys Trp Lys Gly Asn Thr Ser 435 440 445 agg gga caa tac atg gat gat gtc atg gtt ttg gtg gat tca gaa gag 1753 Arg Gly Gln Tyr Met Asp Asp Val Met Val Leu Val Asp Ser Glu Glu 450 455 460 gaa gag gag gag gag gag gag gag gag gaa gat gct gca gta ggg gaa 1801 Glu Glu Glu Glu Glu Glu Glu Glu Glu Glu Asp Ala Ala Val Gly Glu 465 470 475 cag gag gga gca cgt gag aga gag gag ttg cca aaa gaa ata cct aag 1849 Gln Glu Gly Ala Arg Glu Arg Glu Glu Leu Pro Lys Glu Ile Pro Lys 480 485 490 495 cag gac cac att cac aga gtg acc gcc ttg gtg aat ggg aac ata gaa 1897 Gln Asp His Ile His Arg Val Thr Ala Leu Val Asn Gly Asn Ile Glu 500 505 510 cag atg gga aat gga ttc cag gat cta caa gat gac agc agt gag gag 1945 Gln Met Gly Asn Gly Phe Gln Asp Leu Gln Asp Asp Ser Ser Glu Glu 515 520 525 caa agt gac att gtt caa gaa gaa gac agg cca gtc tga agaagaggat 1994 Gln Ser Asp Ile Val Gln Glu Glu Asp Arg Pro Val * 530 535 540 ggtccatggt tgtcttgctc tgaaagcttg gagagctaca ttgaagacga gctcttcatt 2054 cagctttgac tccacctgca cccctggcgg gggcttgcac taacaatgtt tgggtctcag 2114 caaaaaacaa aaccaagcac acacatcttt ccttccatgt attgaaaaac attggtttga 2174 tttgctctaa gttttcccaa tgatgtttaa aagctttgag aaggaaagct gctttggtgt 2234 ctgaggtgcc acttctgctg tgaatcctgg ctttatccag gttgatctac tgtgatagat 2294 gctgatttag agggaacaga ggtcagggaa gcacaagatg gaaaattgca ataacccatg 2354 cactgagact tagaaaatca tccttactag gtaaaatgta ttatgatgca ataagtgcca 2414 actgatattt ctcacgttgg gactggccag gaactgctgc aaagaaaaat aagcagctcc 2474 ttctccatta tttacatttt aagatgtggt ggggggaggt tgggagaaat tagttctgag 2534 gttatcatat gcctttttta aaagataatg gaataaagct atttttaagt 2584 2 1359 DNA Homo sapiens CDS (114)..(1280) 2 atttggccct cgaggccaag aattcggcac gagggctcgg gtggttacgc accctggaag 60 ggaataaaca ttaggaccat agaggacgct ctaggactaa tgctcatcag aaa atg 116 Met 1 act agg agt gct ggc atc cct atg ttc ttt ttt cag atg gga aac att 164 Thr Arg Ser Ala Gly Ile Pro Met Phe Phe Phe Gln Met Gly Asn Ile 5 10 15 ccc ccc aag gca aaa acg ccc cta aga tgt att ctg gag aat tgg gac 212 Pro Pro Lys Ala Lys Thr Pro Leu Arg Cys Ile Leu Glu Asn Trp Asp 20 25 30 caa ttt gac cct cag atg cta aga aag aaa cta ctt ata ttc ttc tgc 260 Gln Phe Asp Pro Gln Met Leu Arg Lys Lys Leu Leu Ile Phe Phe Cys 35 40 45 agt act gcc tgg cca caa tat cct ctt caa ggg gga gaa acc tgg cct 308 Ser Thr Ala Trp Pro Gln Tyr Pro Leu Gln Gly Gly Glu Thr Trp Pro 50 55 60 65 cct aag aga agt ata aat tat aac agc atc tta cag cta gac ctc ttt 356 Pro Lys Arg Ser Ile Asn Tyr Asn Ser Ile Leu Gln Leu Asp Leu Phe 70 75 80 tgt aga aag gag ggc aaa tgg agt gaa gtg cca tat gtg caa act ttc 404 Cys Arg Lys Glu Gly Lys Trp Ser Glu Val Pro Tyr Val Gln Thr Phe 85 90 95 ttt tca tta aga gac aac tca caa tta tgt aaa aag tgt ggt tta tgc 452 Phe Ser Leu Arg Asp Asn Ser Gln Leu Cys Lys Lys Cys Gly Leu Cys 100 105 110 cct aca gga agc cct cag agt cca cct ccc tac ccc agc gtc ccc ccc 500 Pro Thr Gly Ser Pro Gln Ser Pro Pro Pro Tyr Pro Ser Val Pro Pro 115 120 125 ccg act cct tcc tca act aat aag gac ccc cct tta acc caa acg gtc 548 Pro Thr Pro Ser Ser Thr Asn Lys Asp Pro Pro Leu Thr Gln Thr Val 130 135 140 145 caa aag gag ata gac aaa ggg gta aac aat gaa cca aag agt gcc aat 596 Gln Lys Glu Ile Asp Lys Gly Val Asn Asn Glu Pro Lys Ser Ala Asn 150 155 160 att ccc cga tta tgc ccc ctc caa gca gtg aga gga gga gaa ttc ggc 644 Ile Pro Arg Leu Cys Pro Leu Gln Ala Val Arg Gly Gly Glu Phe Gly 165 170 175 cca gcc aga gtg cct gta cct ttt tct ctc tca gac tta aag caa att 692 Pro Ala Arg Val Pro Val Pro Phe Ser Leu Ser Asp Leu Lys Gln Ile 180 185 190 aaa ata gac cta ggt aaa ttc tca gat aac cct gac ggc tat att gat 740 Lys Ile Asp Leu Gly Lys Phe Ser Asp Asn Pro Asp Gly Tyr Ile Asp 195 200 205 gtt tta caa ggg tta gga caa tcc ttt gat ctg aca tgg aga gat ata 788 Val Leu Gln Gly Leu Gly Gln Ser Phe Asp Leu Thr Trp Arg Asp Ile 210 215 220 225 atg tta cta cta aat cag aca cta acc cca aat gag aga agt gcc acc 836 Met Leu Leu Leu Asn Gln Thr Leu Thr Pro Asn Glu Arg Ser Ala Thr 230 235 240 ata act gca gcc cga gag ctt ggc gat ctc tgg tat ctc agt cag gtc 884 Ile Thr Ala Ala Arg Glu Leu Gly Asp Leu Trp Tyr Leu Ser Gln Val 245 250 255 aat gat agg atg aca aca gag gaa aga gaa cga ttc cat aca ggc cag 932 Asn Asp Arg Met Thr Thr Glu Glu Arg Glu Arg Phe His Thr Gly Gln 260 265 270 cag gca gtt ccc agt gca gac cct cat tgg gac aca gaa tca gaa cat 980 Gln Ala Val Pro Ser Ala Asp Pro His Trp Asp Thr Glu Ser Glu His 275 280 285 gga gat tgg tgc tgc aga cat tta cta act tgc gtg ctg gaa gga cta 1028 Gly Asp Trp Cys Cys Arg His Leu Leu Thr Cys Val Leu Glu Gly Leu 290 295 300 305 agg aaa acc agg aag aag gct gtg aat ttt tca gtg atg tcc act gta 1076 Arg Lys Thr Arg Lys Lys Ala Val Asn Phe Ser Val Met Ser Thr Val 310 315 320 aca cag gga aag gaa gaa aat cct act gcc ttt ctg gag aga cta agg 1124 Thr Gln Gly Lys Glu Glu Asn Pro Thr Ala Phe Leu Glu Arg Leu Arg 325 330 335 gag gca ctg agg aag cat acc tcc ctg tca cct gac tct att gaa ggc 1172 Glu Ala Leu Arg Lys His Thr Ser Leu Ser Pro Asp Ser Ile Glu Gly 340 345 350 caa cta atc tta aag att aag ttt atc act cgg tca gct gca gac att 1220 Gln Leu Ile Leu Lys Ile Lys Phe Ile Thr Arg Ser Ala Ala Asp Ile 355 360 365 aga aaa caa act tca aaa gtc cac ctt agg cct gga gca aaa ctt aag 1268 Arg Lys Gln Thr Ser Lys Val His Leu Arg Pro Gly Ala Lys Leu Lys 370 375 380 385 aca ccc tat tga act tggcaacctc ggttttttat aatagagatc aggaggagca 1323 Thr Pro Tyr * gtcggaatgg gacaaacgag attaaaaaaa aaaaaa 1359 3 1746 DNA Homo sapiens CDS (1401)..(1622) misc_feature (1)...(1746) n = a,t,c or g 3 ccactttgta caagaaagct gggtacgcgt aagcttgggc ccctcgaggg atactctaga 60 gcggccgcat tctttttttt tttttttttt ttttgggtgt ggtgatgtat ttattcataa 120 tatattttca gaacacatta ataatggaga ataacactta ttcatatact gaatataact 180 tttcctggag cactctagag cttgtttgga gttggagaat actgccaggc ttttcctaat 240 ctctttggtc tttggaagtg ggcagggttt ctcaaaccaa gtgtcttcca tgggccattg 300 gcaaaggctt cccttcatca gcttggaggg gcagaaagac catggcttca gcacttccat 360 tttggaaaga agtaacaaaa aagtgaatta atgagcaatc ggaaagactc aaagcatttt 420 gtactccaca gttcatttct tcacacaaac gtccattact gcagcgggca tgaaaaccgg 480 cagggtgtta ggctcatggc ctgaagagaa gtcacatcac cagccgatgt tttcatgcaa 540 aaggcaatcg tgatgattca gaacctggtt ctgaatttct ccaggtgtgc tcgtgagctg 600 aaggtcatgc ccattctgtg catcctgtgt ctttctactg gtaaacttgg atgtcatttt 660 agagtatctt ggcaaaatgg tgagaggatc tcactttccc aatatcactc tgtaatgaag 720 ctgcttgggg gatcctccat ttgattgtgg agagaccaag gcaccgtggg ctgaagcaac 780 gaatattaac aacactaaca acaataagga taaagtctaa gtctcttcca aaaaaggcat 840 atccaaaaat aagggtaaag agctggtctt atttcatcca agtgattctg tgcactggaa 900 attgtccttc cgttcctccc tttcattaaa agtgtttata tttctgagtc ggatgatcat 960 ttaaatacat acaatattag caccaaggca gcatattttt ttcccagaga tcacatgaaa 1020 ctgaatactt atttaacata gttaatagtt ggtacaatct gtgatatcac taacatactt 1080 attggctgat acttgcctag aaatgccaaa aatatctttt atacaactct tatagcacct 1140 tgatgatggc tagattgttt taaaaaaatt cattttaaaa aagtaacaat aaaacattta 1200 cagatgaaaa gtaaacaata gtgtaccgtg ataatgaagg atcactttgt catattacta 1260 catgcaaagg cagtcataat agaatcattt tacgtacaaa aatattacat cacaataaat 1320 aatttcaaac ataaatatta aactttacat cattaggata gtctacatat ctacatacac 1380 acatatatgt gtatatatgt atg tgt aga tat gta tat atg tat atg tac 1430 Met Cys Arg Tyr Val Tyr Met Tyr Met Tyr 1 5 10 aca cat tta cac aca caa gca tac aag tca cac aca aac aca cac aca 1478 Thr His Leu His Thr Gln Ala Tyr Lys Ser His Thr Asn Thr His Thr 15 20 25 cat aca cat gca ccc aaa tta agg tgg agg tat tgc att act atc ctt 1526 His Thr His Ala Pro Lys Leu Arg Trp Arg Tyr Cys Ile Thr Ile Leu 30 35 40 cat cca tcc ata atg gct tcc tct tca aag cac ctt agc tat aaa act 1574 His Pro Ser Ile Met Ala Ser Ser Ser Lys His Leu Ser Tyr Lys Thr 45 50 55 cgc acc tcc agg cca gta cca gag gat gga gtg cat ttt cca cag taa 1622 Arg Thr Ser Arg Pro Val Pro Glu Asp Gly Val His Phe Pro Gln * 60 65 70 ccaccgcatt tccctacgac tcgggtacca tccggcgact tcttgatgtc agagacagca 1682 taattccctt gtgatatccg tctggaatta cgcgnctctc gatagtgttc gatgnnggca 1742 ctct 1746 4 1324 DNA Homo sapiens CDS (75)..(374) 4 atttggccct cgaggccaag aattcggcac gaggaaaaag agacaaatta cccagaaacc 60 cctcccttcc ccac atg gag gcc ttg gca aat gtt aat ttt cct aga aaa 110 Met Glu Ala Leu Ala Asn Val Asn Phe Pro Arg Lys 1 5 10 tcc ttc aga cct gaa gac gca gga aaa gaa tct ggc tct cag ggt ggc 158 Ser Phe Arg Pro Glu Asp Ala Gly Lys Glu Ser Gly Ser Gln Gly Gly 15 20 25 ttc tgc gtc ccc gcc gcc agg ccc cag act atg gtc aca ggg ccg tcc 206 Phe Cys Val Pro Ala Ala Arg Pro Gln Thr Met Val Thr Gly Pro Ser 30 35 40 tgt tcc tcc ccg gga ctc cag aat ttc tct cct caa agg aaa gaa aac 254 Cys Ser Ser Pro Gly Leu Gln Asn Phe Ser Pro Gln Arg Lys Glu Asn 45 50 55 60 agg gca tgc gct tgt tgg caa aac gca ggg ccg gct ccc aaa aac ccc 302 Arg Ala Cys Ala Cys Trp Gln Asn Ala Gly Pro Ala Pro Lys Asn Pro 65 70 75 atg tgt gta cga tta aaa gtt ggc cgt ccc cag gcc tcc cag cgc aaa 350 Met Cys Val Arg Leu Lys Val Gly Arg Pro Gln Ala Ser Gln Arg Lys 80 85 90 ctt aaa gag aca ggg ctt tgc tga aaaccaaaca tgggccagct gggcttttta 404 Leu Lys Glu Thr Gly Leu Cys * 95 100 acaacctaga gactttccgg agctgcctgg aacagagcct gcgggaaacg gggcttgcca 464 gagacactca cagtttcctt catggcctgt tttggtcccc taagaatctc cacatcattg 524 tctttcttgt gccttttcct tggtgagcaa cagaaaggga agggttccaa gcctctaaaa 584 atgtgctttg tgatcaggag tgcgctccaa accaaatacg cgcgctgccc tttcgaggcc 644 agtgagctca gcctccaagg ctttaaagcc acatttcagc aagagaaagc gctgagagct 704 cgcaggttca ttaaagaagg caaagcactg gtttctctcc ttagaaaagt aggtttcttg 764 gcttgatgta gactggcttg ctttgatttt tagtgaaggg aatgtacgta aaacaaaata 824 gggcttggct ggtcaaagga gacaagcagg atggatggat ggatggatga atagatagat 884 ggtgtttgca tgtaaattgc agagaaaaca aaaccaaagc tgattggaaa caattaattg 944 tgggtgtctg agggggaagg tcgcagcttt gggcagcttt gagaagcggt acaagagctc 1004 tgtgcctgtg tgtccagccc tggagccagc cagtgcattt attttaagct cttagaagca 1064 actccttggc ccaggaatgc gtgacccctg agatgggtcc acgcatctct ctacacgtcc 1124 ttctctccgt gggatactgg actcgtgcct ctgcgcccat tctcttctca cgcatatcca 1184 tgagctttaa tttcactttc tgatcacggt acgtccataa agccagtatt acacttaaat 1244 gaagtattct tttttgtaat cgtttttttt agaaggtaaa caaatttaat aaagctacca 1304 ataatgttaa aaaaaaaaaa 1324 5 2307 DNA Homo sapiens CDS (1612)..(2184) 5 gcaatttcat aatatggtaa tttttaatat taaaagtaaa ttgtaaatgt gtctttataa 60 acaatatgca taaaatagat catattctaa acccttttct ttttaaaacg ctttttcaca 120 gtaaatttct tatggtcaga ttttccctca gaatagtgca actggaagaa gggaaatgtt 180 ggcagtggct caggactctc tgctagtaca agtccttgta gatctcctgc aggagcgggt 240 gaagactcat gtctgtctcc gtcttcttga tcacctgcag tagctgcacg tgttccgtga 300 caatctgtct gaggtctgtc attttctgga gcagcttggc aaacagctgt gaggactcag 360 ggtggttcag cttcagctgg agctccaggg cttgtagcag gttgtcttga atgtcttcaa 420 tgggcttcac attcagcaaa cctgggcggt ctccactgag aataatgaca gcaataaata 480 ttgccaagtc gctgtcatct aattccagtg cattgaactt cacagcaaac tcaaacttgg 540 gctccataaa gtcaccaaaa ggctttcgca ggctctttag aaactccctt gtcatgaagc 600 cttggccctc ggatatgaga accccatctt tattcatcaa ggaggccagc attgtgtaaa 660 tgatctcgtg gactccatat ttgaggagag ttacttggtc gttcaagtca agatttacaa 720 aaccaggaat gcttttggca tactctgtga tctcctgcac agcctccacg gagcgaaact 780 ggcagccctg aaagatgcgg atggccacct ctttgctctg ctcctgcagg ggggtgatgt 840 gtttgaactt gattttatct tctcccatca ttaaggaatt catgtcatag ataacgaatg 900 gtgatttgtc tgttgtcttt cctgtcaaga tcgccctcgc ctttgctttg gtcagcggga 960 aggactttat gtatgagtca tacaaatgtt ttgccagggc ctgacggagg tcagcggact 1020 ctggattcag ctggtcgata tcactggaga tctccgccaa cagcttctcc ttctcggcct 1080 gtgcgatccg cccaaacctg atggcattat gagacatccc cactgcaagg catttctgaa 1140 accgacagta ctgacattta tttctacttt ttttgtggat ccgacagtta agatcacatc 1200 tgtcatagat aagcttcaat ctgattgttc tccggaagaa acccttgcat ccttcacaag 1260 catgaactcc atagtgaaat ccagaagctt tatctccaca gacacgacat tcaattgcca 1320 tgagggagtt ggaaggctct tcatgaggct tattgtagag ctgagtcttc tcagaataat 1380 aaggtggaga tgcaggctcc actttgattg cactttggta ctcttgaagt ttcaggtcat 1440 acttgtaatc tgcaaccact ggatctgttc ttgtgaatgg aatgtcttcg taatgtggag 1500 tagaaatgct ggagaagtca acagtagtga agggcttgat atcaaaggag tgggagtggt 1560 cttccattac ggagagatcc acggagctga tcccaaagtt ggtgggccag a atg cga 1617 Met Arg 1 tct ctg tgt caa cca tgg tca ttt ctg cgg cca cgg cgg cgt ggc gcc 1665 Ser Leu Cys Gln Pro Trp Ser Phe Leu Arg Pro Arg Arg Arg Gly Ala 5 10 15 cct ctc cgg tgt cct cga ggc cga ccc aag ccc ccc agg cgg cgg ctg 1713 Pro Leu Arg Cys Pro Arg Gly Arg Pro Lys Pro Pro Arg Arg Arg Leu 20 25 30 cgg ctc ggg ctc ggg aat tcc cag act cag aga gaa ccc acc atg gtg 1761 Arg Leu Gly Leu Gly Asn Ser Gln Thr Gln Arg Glu Pro Thr Met Val 35 40 45 50 ctg tct cct gcc gac aag acc aac gtc aag gcc gcc tgg ggt aag gtc 1809 Leu Ser Pro Ala Asp Lys Thr Asn Val Lys Ala Ala Trp Gly Lys Val 55 60 65 ggc gcg cac gct ggc gag tat ggt gcg gag gcc ctg gag agg atg ttc 1857 Gly Ala His Ala Gly Glu Tyr Gly Ala Glu Ala Leu Glu Arg Met Phe 70 75 80 ctg tcc ttc ccc acc acc aag acc tac ttc ccg cac ttc gac ctg agc 1905 Leu Ser Phe Pro Thr Thr Lys Thr Tyr Phe Pro His Phe Asp Leu Ser 85 90 95 cac ggc tct gcc cag gtt aag ggc cac ggc aag aag gtg gcc gac gcg 1953 His Gly Ser Ala Gln Val Lys Gly His Gly Lys Lys Val Ala Asp Ala 100 105 110 ctg acc aac gcc gtg gcg cac gtg gac gac atg ccc aac gcg ctg tcc 2001 Leu Thr Asn Ala Val Ala His Val Asp Asp Met Pro Asn Ala Leu Ser 115 120 125 130 gcc ctg agc gac ctg cac gcg cac aag ctt cgg gtg gac ccg gtc aac 2049 Ala Leu Ser Asp Leu His Ala His Lys Leu Arg Val Asp Pro Val Asn 135 140 145 ttc aag ctc cta agc cac tgc ctg ctg gtg acc ctg gcc gcc cac ctc 2097 Phe Lys Leu Leu Ser His Cys Leu Leu Val Thr Leu Ala Ala His Leu 150 155 160 ccc gcc gag ttc acc cct gcg gtg cac gcc tcc ctg gac aag ttc ctg 2145 Pro Ala Glu Phe Thr Pro Ala Val His Ala Ser Leu Asp Lys Phe Leu 165 170 175 gct tct gtg agc acc gtg ctg acc tcc aaa tac cgt taa gctggagcct 2194 Ala Ser Val Ser Thr Val Leu Thr Ser Lys Tyr Arg * 180 185 190 cggtggccat gcttcttgcc ccttgggcct ccccccagcc cctcctcccc ttcctgcacc 2254 cgtacccccg tggtctttga ataaagtctg agtgggcggc aaaaaaaaaa aaa 2307 6 1150 DNA Homo sapiens CDS (29)..(625) misc_feature (1)...(1150) n = a,t,c or g 6 gccggccnnt ttgataggca gacattgt atg gca gta ccc agc tgg cta gcg 52 Met Ala Val Pro Ser Trp Leu Ala 1 5 ttt aaa ctt aag ctt ggt acc gag ctc gga tcc act agt cca gtg tgg 100 Phe Lys Leu Lys Leu Gly Thr Glu Leu Gly Ser Thr Ser Pro Val Trp 10 15 20 tgg aat tcg gcc tcc aac ttt aag aag gca aac atg gca tca agt tct 148 Trp Asn Ser Ala Ser Asn Phe Lys Lys Ala Asn Met Ala Ser Ser Ser 25 30 35 40 cag cga aaa aga atg agc cct aag cct gag ctt act gaa gag caa aag 196 Gln Arg Lys Arg Met Ser Pro Lys Pro Glu Leu Thr Glu Glu Gln Lys 45 50 55 cag gag atc cgg gaa gct ttt gat ctt ttc gat gcg gat gga act ggc 244 Gln Glu Ile Arg Glu Ala Phe Asp Leu Phe Asp Ala Asp Gly Thr Gly 60 65 70 acc ata gat gtt aaa gaa ctg aag gtg gca atg agg gcc ctg ggc ttt 292 Thr Ile Asp Val Lys Glu Leu Lys Val Ala Met Arg Ala Leu Gly Phe 75 80 85 gaa ccc aag aaa gaa gaa att aag aaa atg ata agt gaa att gat aag 340 Glu Pro Lys Lys Glu Glu Ile Lys Lys Met Ile Ser Glu Ile Asp Lys 90 95 100 gaa ggg aca gga aaa atg aac ttt ggt gac ttt tta act gtg atg acc 388 Glu Gly Thr Gly Lys Met Asn Phe Gly Asp Phe Leu Thr Val Met Thr 105 110 115 120 cag aaa atg tct gag aaa gat act aaa gaa gaa atc ctg aaa gct ttc 436 Gln Lys Met Ser Glu Lys Asp Thr Lys Glu Glu Ile Leu Lys Ala Phe 125 130 135 aag ctc ttt gat gat gat gaa act ggg aag att tcg ttc aaa aat ctg 484 Lys Leu Phe Asp Asp Asp Glu Thr Gly Lys Ile Ser Phe Lys Asn Leu 140 145 150 aaa cgc gtg gcc aag gag ttg ggt gag aac ctg act gat gag gag ctg 532 Lys Arg Val Ala Lys Glu Leu Gly Glu Asn Leu Thr Asp Glu Glu Leu 155 160 165 cag gaa atg att gat gaa gct gat cga gat gga gat gga gag gtc agt 580 Gln Glu Met Ile Asp Glu Ala Asp Arg Asp Gly Asp Gly Glu Val Ser 170 175 180 gag caa gag ttc ctg cgc atc atg aaa aag acc agc ctc tat taa gat 628 Glu Gln Glu Phe Leu Arg Ile Met Lys Lys Thr Ser Leu Tyr * 185 190 195 cagtgtcttc tttttctact gcaagcacat gtaactagat ttagtgcctg ccatggtgtg 688 aaatctggct tttgagaaca caaacttttc ccccacggac ctccctttat cactttaata 748 gtgaccttga gcctatttta gccgtttgga agtgttcttt gatattacag ttctttgtaa 808 aatgacctgc gaattaccct aattctcaaa agcaaaacaa gagcacacaa gcgtgaagaa 868 aaggatctta aagctttgag cacctgccat tttgccttgc atcgtttccc tcgtcatgca 928 tttccacata tccacaaaca cagaacgact ttagacaagc acatgttaca cctgtgttgc 988 cacaagcagt cattcttgac ggctccagtt tttatttgac acttgagttt agttttctct 1048 tttataaacc cagtgaactc ctgcactggc atttggatgt gtgttaatgc tatttgtttt 1108 gtcttaaaag taaaaccttt ctcagtttga aaaaaaaaaa aa 1150 7 1156 DNA Homo sapiens CDS (72)..(938) 7 tttgtatcgc ctgcggcacc gggccggaat tcccgggtcg acccacgcgt ccgcccacgc 60 gtccgagctg g atg tcc agg ctg cgg gcg ctg ctg ggc ctc ggg ctg ctg 110 Met Ser Arg Leu Arg Ala Leu Leu Gly Leu Gly Leu Leu 1 5 10 gtt gcg ggc tcg cgc ctg ccg cgg atc aaa agc cag acc atc gcc tgt 158 Val Ala Gly Ser Arg Leu Pro Arg Ile Lys Ser Gln Thr Ile Ala Cys 15 20 25 cgc tcg gga ccc acc tgg tgg gga ccg cag cgg ctg aac tcg ggt ggc 206 Arg Ser Gly Pro Thr Trp Trp Gly Pro Gln Arg Leu Asn Ser Gly Gly 30 35 40 45 cgc tgg gac tca gag gtc atg gcg agc acg gtg gtg aag tac ctg agc 254 Arg Trp Asp Ser Glu Val Met Ala Ser Thr Val Val Lys Tyr Leu Ser 50 55 60 cag gag gag gcc cag gcc gtg gac cag gag cta ttt aac gaa tac cag 302 Gln Glu Glu Ala Gln Ala Val Asp Gln Glu Leu Phe Asn Glu Tyr Gln 65 70 75 ttc agc gtg gac caa ctt atg gaa ctg gcc ggg ctg agc tgt gct aca 350 Phe Ser Val Asp Gln Leu Met Glu Leu Ala Gly Leu Ser Cys Ala Thr 80 85 90 gcc atc gcc aag gca tat ccc ccc acg tcc atg tcc agg agc ccc cct 398 Ala Ile Ala Lys Ala Tyr Pro Pro Thr Ser Met Ser Arg Ser Pro Pro 95 100 105 act gtc ctg gtc atc tgt ggc ccg ggg aat aat gga gga gat ggt ctg 446 Thr Val Leu Val Ile Cys Gly Pro Gly Asn Asn Gly Gly Asp Gly Leu 110 115 120 125 gtc tgt gct cga cac ctc aaa ctc ttt ggc tac gag cca acc atc tat 494 Val Cys Ala Arg His Leu Lys Leu Phe Gly Tyr Glu Pro Thr Ile Tyr 130 135 140 tac ccc aaa agg cct aac aag ccc ctc ttc act gca ttg gtg acc cag 542 Tyr Pro Lys Arg Pro Asn Lys Pro Leu Phe Thr Ala Leu Val Thr Gln 145 150 155 tgt cag aaa atg gac atc cct ttc ctt ggg gaa atg ccc gca gag ccc 590 Cys Gln Lys Met Asp Ile Pro Phe Leu Gly Glu Met Pro Ala Glu Pro 160 165 170 atg acg att gat gaa ctg tat gag ctg gtg gtg gat gcc atc ttt ggc 638 Met Thr Ile Asp Glu Leu Tyr Glu Leu Val Val Asp Ala Ile Phe Gly 175 180 185 ttc agc ttc aag ggc gat gtt cgg gaa ccg ttc cac agc atc ctg agt 686 Phe Ser Phe Lys Gly Asp Val Arg Glu Pro Phe His Ser Ile Leu Ser 190 195 200 205 gtc ctg aag gga ctc act gtg ccc att gcc agc atc gac att ccc tca 734 Val Leu Lys Gly Leu Thr Val Pro Ile Ala Ser Ile Asp Ile Pro Ser 210 215 220 gga tgg gac gtg gag aag gga aat gct gga ggg atc cag cca gac ttg 782 Gly Trp Asp Val Glu Lys Gly Asn Ala Gly Gly Ile Gln Pro Asp Leu 225 230 235 ctc atc tcc ctc aca gcc ccc aaa aaa tct gca acc cag ttt acc ggt 830 Leu Ile Ser Leu Thr Ala Pro Lys Lys Ser Ala Thr Gln Phe Thr Gly 240 245 250 cgc tac cat tac ctg ggg ggt cgt ttt gtg cca cct gct ctg gaa aag 878 Arg Tyr His Tyr Leu Gly Gly Arg Phe Val Pro Pro Ala Leu Glu Lys 255 260 265 aag tac cag ctg aac ctg cca ccc tac cct gac act gag tgt gtc tat 926 Lys Tyr Gln Leu Asn Leu Pro Pro Tyr Pro Asp Thr Glu Cys Val Tyr 270 275 280 285 cgt ctg cag tga ggg aaggtgggtg ggtattctcc ccaataaaga cttagagccc 981 Arg Leu Gln * ctctcttcca gaactgtgga ttcctgggag ctcctctggc aataaaagtc agtgaatggt 1041 ggaagtcaga gagcaaccct ggggattggg tgccatctct ctaggggtaa cacaaagggc 1101 aagaggttgc tatggtattt ggaaacaatg aaaatggact gttaaaaaaa aaaaa 1156 8 2019 DNA Homo sapiens CDS (1511)..(1849) 8 ccactttgta caagaaagct gggtacgcgt aagcttgggc ccctcgaggg atactctaga 60 gcggccgccc tttttttttt tttttaaaaa ttactctttt acttttatta caataaataa 120 ttatcaataa tagaattaaa caattttcaa ttaaaaccta ctgcattact ttggggtttc 180 acagcagcag aaacaaacat aaatccagtt gaaagggcaa ggcttccaga atccagtgac 240 aagaaacagt ctggtcttga ttattcgggc tagcaatggg aaacactgat acagataatg 300 caaaaacaat gaaatgcatc ggcatactct ctttgtacat cacattatct gacactttaa 360 aatattccag ctaagtaatt taagcaagcc atgaagctct gtttctgcaa cagttagagt 420 tctcccccag caagcccgca gcacaactgc tcccagagcc accctctggc cagaaacggg 480 ccccatcatc atgcagacct agaagcctcc accctggtgg aagcagccat ctttctcaaa 540 gctctttctg gctcacacaa cccatggtta aaggaaaatg ggaaagtgac atatttaaag 600 ggcctttctc gaggactgag atgaactgga agacagacag actgtggctc cagatcagga 660 agaggcttca gagtaagggc cacatgcaga tgaactccac atgaagaaac tatctgataa 720 aggctgacca ttttgctgat aatcaagcag actgcatgta tatatgaata tatcatacat 780 acatatgtag tgaatatatg tgtacatatt aaataggcat acacacacat cacacacaac 840 cagataaaat aaatggtaca tacattgcta ctatgaacac tgcacgtccc agacagacca 900 atgactaata tgttcaatta aactacttga attaaactac tcttcctctc cccaaaatat 960 tctgcttgca gcaaacatat tccagttgct caagcggtgt tgtttctagg ttcctgagaa 1020 ggaatggaat cgtcctcttg tttcagaaca ctacagaaag ccaactgcaa caggaccaag 1080 ctaaacaatt catatttgat ttggccatga ttcctccacc tattcttagt cacagggcat 1140 gaaaccttac tcagaaagat atcaatttct ttttctacaa ctggctacaa atttactgta 1200 ttatgttaga tggaggggac tgggggaagg cgggcagcag ggagtttaca tgttggcaat 1260 cattcattgc ctttcccttt acccagagaa aatgctactt taaaaaaaaa aacacccaga 1320 aatttagagt tcaataatga attttgcttt cttggcacat ttttgaaatg atcatatcat 1380 tacatgtagc taggtcttta tctcctgaat gctcctctag ggaggcaagt tatctaaaca 1440 acaaaataac ctacaaaaaa agttaatatt gtgagcagtc tcaatttgta gttattaaac 1500 tcaaagtcta atg ctg aaa ggc aac agt aat tta aac aga ttt gtt tat 1549 Met Leu Lys Gly Asn Ser Asn Leu Asn Arg Phe Val Tyr 1 5 10 ttt tat tat tat ttt ttg aga tgg agt ctt gct ctg tca ctc tgg ctg 1597 Phe Tyr Tyr Tyr Phe Leu Arg Trp Ser Leu Ala Leu Ser Leu Trp Leu 15 20 25 gag tgc agt ggc aca atc tcc gct cac tgc aat ctc cat ctc cca ggt 1645 Glu Cys Ser Gly Thr Ile Ser Ala His Cys Asn Leu His Leu Pro Gly 30 35 40 45 tca agt gat tct cct gcc tca gcc tcc cca gta act ggg att aca ggc 1693 Ser Ser Asp Ser Pro Ala Ser Ala Ser Pro Val Thr Gly Ile Thr Gly 50 55 60 aca tgc cac cat gcc cag cta att ttt ttg tat ttt tat tac aga cgg 1741 Thr Cys His His Ala Gln Leu Ile Phe Leu Tyr Phe Tyr Tyr Arg Arg 65 70 75 ggt ttc gcc atg ttg ctc agg ttg gtg tcg aac tcc tgg gct caa gca 1789 Gly Phe Ala Met Leu Leu Arg Leu Val Ser Asn Ser Trp Ala Gln Ala 80 85 90 atc cac ctg cct tgg ctt ccc aaa gtg ctg gga tta cag gca cct gcc 1837 Ile His Leu Pro Trp Leu Pro Lys Val Leu Gly Leu Gln Ala Pro Ala 95 100 105 cca gat tta taa tgc tattcacaga tcttgcagaa ttataacagg ctccttctac 1892 Pro Asp Leu * 110 aacttggtta gtgacatcaa gtactaacta tatatgttcc aggtcaagaa cttactcttg 1952 agatattcaa aaagtgcttg tcaagaatat caggaatcta gaatttatgg caaattgtat 2012 atatttt 2019 9 1368 DNA Homo sapiens CDS (90)..(1175) 9 aaggatcctt aattaaatta atcccccccc cccggtgagc cgcaaccttt ccaagggagt 60 ggttgtgtga tcgccatctt agggaaaag atg ttc tcg tcc gtg gcg cac ctg 113 Met Phe Ser Ser Val Ala His Leu 1 5 gcg cgg gcg aac ccc ttc aac acg cca cat ctg cag ctg gtg cac gat 161 Ala Arg Ala Asn Pro Phe Asn Thr Pro His Leu Gln Leu Val His Asp 10 15 20 ggt ctc ggg gac ctc cgc agc agc tcc cca ggg ccc acg ggc cag ccc 209 Gly Leu Gly Asp Leu Arg Ser Ser Ser Pro Gly Pro Thr Gly Gln Pro 25 30 35 40 cgc cgc cct cgc aac ctg gca gcc gcc gcc gtg gaa gag tac agt tgt 257 Arg Arg Pro Arg Asn Leu Ala Ala Ala Ala Val Glu Glu Tyr Ser Cys 45 50 55 gaa ttt ggc tcc gcg aag tat tat gca ctg tgt ggc ttt ggt ggg gtc 305 Glu Phe Gly Ser Ala Lys Tyr Tyr Ala Leu Cys Gly Phe Gly Gly Val 60 65 70 tta agt tgt ggt ctg aca cac act gct gtg gtt ccc ctg gat tta gtg 353 Leu Ser Cys Gly Leu Thr His Thr Ala Val Val Pro Leu Asp Leu Val 75 80 85 aaa tgc cgt atg cag gtg gac ccc caa aag tac aag ggc ata ttt aac 401 Lys Cys Arg Met Gln Val Asp Pro Gln Lys Tyr Lys Gly Ile Phe Asn 90 95 100 gga ttc tca gtt aca ctt aaa gag gat ggt gtt cgt ggt ttg gct aaa 449 Gly Phe Ser Val Thr Leu Lys Glu Asp Gly Val Arg Gly Leu Ala Lys 105 110 115 120 gga tgg gct ccg act ttc ctt ggc tac tcc atg cag gga ctc tgc aag 497 Gly Trp Ala Pro Thr Phe Leu Gly Tyr Ser Met Gln Gly Leu Cys Lys 125 130 135 ttt ggc ttt tat gaa gtc ttt aaa gtc ttg tat agc aat atg ctt gga 545 Phe Gly Phe Tyr Glu Val Phe Lys Val Leu Tyr Ser Asn Met Leu Gly 140 145 150 gag gag aat act tat ctc tgg cgc aca tca cta tat ttg gct gcc tct 593 Glu Glu Asn Thr Tyr Leu Trp Arg Thr Ser Leu Tyr Leu Ala Ala Ser 155 160 165 gcc agt gct gaa ttc ttt gct gac att gcc ctg gct cct atg gaa gct 641 Ala Ser Ala Glu Phe Phe Ala Asp Ile Ala Leu Ala Pro Met Glu Ala 170 175 180 gct aag gtt cga att caa acc cag cca ggt tat gcc aac act ttg agg 689 Ala Lys Val Arg Ile Gln Thr Gln Pro Gly Tyr Ala Asn Thr Leu Arg 185 190 195 200 gat gca gct ccc aaa atg tat aag gaa gaa ggc cta aaa gca ttc tac 737 Asp Ala Ala Pro Lys Met Tyr Lys Glu Glu Gly Leu Lys Ala Phe Tyr 205 210 215 aag ggg gtt gct cct ctc tgg atg aga cag ata cca tac acc atg atg 785 Lys Gly Val Ala Pro Leu Trp Met Arg Gln Ile Pro Tyr Thr Met Met 220 225 230 aag ttc gcc tgc ttt gaa cgt act gtt gaa gca ctg tac aag ttt gtg 833 Lys Phe Ala Cys Phe Glu Arg Thr Val Glu Ala Leu Tyr Lys Phe Val 235 240 245 gtt cct aag ccc cgc agt gaa tgt tca aag cca gag cag ctg gtt gta 881 Val Pro Lys Pro Arg Ser Glu Cys Ser Lys Pro Glu Gln Leu Val Val 250 255 260 aca ttt gta gca ggt tac ata gct gga gtc ttt tgt gca att gtt tct 929 Thr Phe Val Ala Gly Tyr Ile Ala Gly Val Phe Cys Ala Ile Val Ser 265 270 275 280 cac cct gct gat tct gtg gta tct gtg ttg aat aaa gaa aaa ggt agc 977 His Pro Ala Asp Ser Val Val Ser Val Leu Asn Lys Glu Lys Gly Ser 285 290 295 agt gct tct ctg gtc ctc aag aga ctt gga ttt aaa ggt gta tgg aag 1025 Ser Ala Ser Leu Val Leu Lys Arg Leu Gly Phe Lys Gly Val Trp Lys 300 305 310 gga ctg ttt gcc cgt atc atc atg att ggt acc ctg act gca cta cag 1073 Gly Leu Phe Ala Arg Ile Ile Met Ile Gly Thr Leu Thr Ala Leu Gln 315 320 325 tgg ttt atc tat gac tcc gtg aag gtc tac ttc aga ctt cct cgc cct 1121 Trp Phe Ile Tyr Asp Ser Val Lys Val Tyr Phe Arg Leu Pro Arg Pro 330 335 340 cct cca ccc gag atg cca gag tct ctg aag aag aag ctt ggg tta act 1169 Pro Pro Pro Glu Met Pro Glu Ser Leu Lys Lys Lys Leu Gly Leu Thr 345 350 355 360 cag tag ttagatcaaa gcaaatgtgg actgaatctg cttgttgatc agtgttgaag 1225 Gln * aaagtgcaaa aggaactttt atatatttga cagtgtagga aattgtctat tcctgatata 1285 attactgtag tactcttgct taaggcaaga gtttcagatt tactgttgaa ataaacccaa 1345 ctcttcatga aaaaaaaaaa aaa 1368 10 894 DNA Homo sapiens CDS (364)..(603) 10 cagattcttt gtcctactga ccaaattccc ccaagttcag aatttgcaga ttttatagca 60 ggtggtattc ttttccaaag atatcttgca ttattcatgt cattatggag caaatataaa 120 gttagaagct gaccataccc tgggggtgta gcaattcctc caggggcctc gagctcctgg 180 ttctcgcact gatccagcaa ctttttgaaa ctaaaggcgc tttccgccat caccgccact 240 ggcatcttcg cggccggcct cgccgttgca ccgtccggac agccaaacct gggctggacg 300 tggttttgtc tgctgcgccc gctcttcgcg ctctcgtttc attttctgca gcgcgccagc 360 agg atg gcc cac aag cag atc tac tac tcg gac aag tac ttc gac gaa 408 Met Ala His Lys Gln Ile Tyr Tyr Ser Asp Lys Tyr Phe Asp Glu 1 5 10 15 cac tac gag tac cgg cat gtt atg tta ccc aga gaa ctt tcc aaa caa 456 His Tyr Glu Tyr Arg His Val Met Leu Pro Arg Glu Leu Ser Lys Gln 20 25 30 gta cct aaa act cat ctg atg tct gaa gag gag tgg agg aga ctt ggt 504 Val Pro Lys Thr His Leu Met Ser Glu Glu Glu Trp Arg Arg Leu Gly 35 40 45 gtc caa cag agt cta ggc tgg gtt cat tac atg att cat gag cca gaa 552 Val Gln Gln Ser Leu Gly Trp Val His Tyr Met Ile His Glu Pro Glu 50 55 60 cca cat att ctt ctc ttt aga cga cct ctt cca aaa gat caa caa aaa 600 Pro His Ile Leu Leu Phe Arg Arg Pro Leu Pro Lys Asp Gln Gln Lys 65 70 75 tga agtt tatctgggga tcgtcaaatc tttttcaaat ttaatgtata tgtgtatata 657 * 80 aggtagtatt cagtgaatac ttgagaaatg tacaaatctt tcatccatac ctgtgcatga 717 gctgtattct tcacagcaac agagctcagt taaatgcaac tgcaagtagg ttactgtaag 777 atgtttaaga taaaagttct tccagtcagt ttttctctta agtgcctgtt tgagtttact 837 gaaacagttt acttttgttc aataaagttt gtatgttgca tttaaaaaaa aaaaaaa 894 11 2248 DNA Homo sapiens CDS (190)..(927) 11 aaggatcctt aattaaatta atcccccccc cccccccccg agctaaagcc aaaagcagat 60 caaagtggtg ggactcgcgt cgcggccgcg gagacgtgaa gctctcgatg ctcctcccgc 120 tgcgggtcgg cgctcgccct cgctctcctc gccctccgcc ccggccccgg ccccggcccc 180 gcgcccgcc atg gag aag act gag ctg atc cag aag gcc aag ctg gcc 228 Met Glu Lys Thr Glu Leu Ile Gln Lys Ala Lys Leu Ala 1 5 10 gag cag gcc gag cgc tac gac gac atg gcc acc tgc atg aag gca gtg 276 Glu Gln Ala Glu Arg Tyr Asp Asp Met Ala Thr Cys Met Lys Ala Val 15 20 25 acc gag cag ggc gcc gag ctg tcc aac gag gag cgc aac ctg ctc tcc 324 Thr Glu Gln Gly Ala Glu Leu Ser Asn Glu Glu Arg Asn Leu Leu Ser 30 35 40 45 gtg gcc tac aag aac gtg gtc ggg ggc cgc agg tcc gcc tgg agg gtc 372 Val Ala Tyr Lys Asn Val Val Gly Gly Arg Arg Ser Ala Trp Arg Val 50 55 60 atc tct agc atc gag cag aag acc gac acc tcc gac aag aag ttg cag 420 Ile Ser Ser Ile Glu Gln Lys Thr Asp Thr Ser Asp Lys Lys Leu Gln 65 70 75 ctg att aag gac tat cgg gag aaa gtg gag tcc gag ctg aga tcc atc 468 Leu Ile Lys Asp Tyr Arg Glu Lys Val Glu Ser Glu Leu Arg Ser Ile 80 85 90 tgc acc acg gtg ctg gaa ttg ttg gat aaa tat tta ata gcc aat gca 516 Cys Thr Thr Val Leu Glu Leu Leu Asp Lys Tyr Leu Ile Ala Asn Ala 95 100 105 act aat cca gag agt aag gtc ttc tat ctg aaa atg aag ggt gat tac 564 Thr Asn Pro Glu Ser Lys Val Phe Tyr Leu Lys Met Lys Gly Asp Tyr 110 115 120 125 ttc cgg tac ctt gct gaa gtt gcg tgt ggt gat gat cga aaa caa acg 612 Phe Arg Tyr Leu Ala Glu Val Ala Cys Gly Asp Asp Arg Lys Gln Thr 130 135 140 ata gat aat tcc caa gga gct tac caa gag gca ttt gat ata agc aag 660 Ile Asp Asn Ser Gln Gly Ala Tyr Gln Glu Ala Phe Asp Ile Ser Lys 145 150 155 aaa gag atg caa ccc aca cac cca atc cgc ctg ggg ctt gct ctt aac 708 Lys Glu Met Gln Pro Thr His Pro Ile Arg Leu Gly Leu Ala Leu Asn 160 165 170 ttt tct gta ttt tac tat gag att ctt aat aac cca gag ctt gcc tgc 756 Phe Ser Val Phe Tyr Tyr Glu Ile Leu Asn Asn Pro Glu Leu Ala Cys 175 180 185 acg ctg gct aaa acg gct ttt gat gag gcc att gct gaa ctt gat aca 804 Thr Leu Ala Lys Thr Ala Phe Asp Glu Ala Ile Ala Glu Leu Asp Thr 190 195 200 205 ctg aat gaa gac tca tac aaa gac agc acc ctc atc atg cag ttg ctt 852 Leu Asn Glu Asp Ser Tyr Lys Asp Ser Thr Leu Ile Met Gln Leu Leu 210 215 220 aga gac aac cta aca ctt tgg aca tca gac agt gca gga gaa gaa tgt 900 Arg Asp Asn Leu Thr Leu Trp Thr Ser Asp Ser Ala Gly Glu Glu Cys 225 230 235 gat gcg gca gaa ggg gct gaa aac taa atcca tacagggtgt catccttctt 952 Asp Ala Ala Glu Gly Ala Glu Asn * 240 245 tccttcaaga aaccttttta cacatctcca ttccttattc cacttggatt tcctatagca 1012 aagaaaccca ttcatgtgta tggaatcaac tgtttatagt cttttcacac tgcagctttg 1072 ggaaaacttc attccttgat ttgtgtttgt cttggccttc ctggtgtgca gtactgctgt 1132 agaaaagtat taatagcttc atttcatata aacataagta actcccaaac acttatgtag 1192 aggactaaaa atgtatctgg tatttaagta atctgaacca gttctgcaag tgactgtgtt 1252 ttgtattact gtgaaaataa gaaaatgtag ttaattacaa tttaaagagt attccacata 1312 acttcttaat ttctacattc cctcccttac tcttcggggg tttcctttca gtaagcaact 1372 tttccatgct cttaatgtat tcctttttag taggaatccg gaagtattag attgaatgga 1432 aaagcacttg ccatctctgt ctaggggtca caaattgaaa tggctcctgt atcacatacg 1492 gaggtcttgt gtatctgtgg caacagggag tttccttatt cactctttat ttgctgctgt 1552 ttaagttgcc aacctcccct cccaataaaa attcacttac acctcctgcc tttgtagttc 1612 tggtattcac tttactatgt gatagaagta gcatgttgct gccagaatac aagcattgct 1672 tttggcaaat taaagtgcat gtcatttctt aatacactag aaaggggaaa taaattaaag 1732 tacacaagtc caagtctaaa actttagtac ttttccatgc agatttgtgc acatgtgaga 1792 gggtgtccag tttgtctagt gattgttatt tagagagttg gaccactatt gtgtgttgct 1852 aatcattgac tgtagtccca aaaaagcctt gtgaaaatgt tatgccctat gtaacagcag 1912 agtaacataa aataaaagta cattttataa accatttact atggctttgt aacaattgca 1972 tacccatatt ttaagggaca ggtgaattta ctactttcta aagtttattg atacttccct 2032 tttatgtaaa atgtagtagt gatacctata tttccacatt gtgcattgtg acacacttgt 2092 ctagggatgc ctggaagtgt ataaaattgg actgcatttc ttagagtgtt ttactataga 2152 tcagtctcat gggccatctc ttcctcagat gtaaatgata tctggttaag tgttatatgg 2212 aataaagtgg acattttaaa actaaaaaaa aaaaaa 2248 12 1739 DNA Homo sapiens CDS (466)..(1566) 12 cctgattgcc cctcctggag gctcgctgtt aaacttacgc ttggtaccga gctcggatcc 60 actagtccag tgtggtggaa ttcgtgattc tgactgaata caggccctgg acccttccct 120 caagtctcac cagttctgct ctcccatcaa gcttcagatg ccatgttgta ctgggggaat 180 gtagcccttg tgctccccac cccctacctc cacctgagcc tcaccctgct gttgagccct 240 gagtggctag gggaaatggg aagaggattg ccatggcctg gccatcttgt tgctgcttgg 300 ttagatcata tagctaatga attaggcagg ggagctattt tttgaagatg atgaactaaa 360 tgttgaagac aagtttgaga tctgtaaaat tttttggctt tcacccccaa ccagtgacca 420 aagacttgac cactcaaagt ccagctcccc agaacactgc tcgac atg gac acc 474 Met Asp Thr 1 ggt gtg att gaa ggt gga tta aat gtc act ctc acc atc cgg cta ctt 522 Gly Val Ile Glu Gly Gly Leu Asn Val Thr Leu Thr Ile Arg Leu Leu 5 10 15 atg cat gga aag gaa gtt ggc agt atc atc gga aag aaa gga gaa tca 570 Met His Gly Lys Glu Val Gly Ser Ile Ile Gly Lys Lys Gly Glu Ser 20 25 30 35 gtt aag aag atg cgc gag gag agt ggt gca cgt atc aac atc tca gaa 618 Val Lys Lys Met Arg Glu Glu Ser Gly Ala Arg Ile Asn Ile Ser Glu 40 45 50 ggg aat tgt cct gag aga att atc act ttg gct gga ccc act aat gcc 666 Gly Asn Cys Pro Glu Arg Ile Ile Thr Leu Ala Gly Pro Thr Asn Ala 55 60 65 atc ttc aaa gcc ttt gct atg atc att gac aaa ctg gaa gag gac ata 714 Ile Phe Lys Ala Phe Ala Met Ile Ile Asp Lys Leu Glu Glu Asp Ile 70 75 80 agc agc tct atg acc aat agc aca gct gcc agt aga ccc ccg gtc acc 762 Ser Ser Ser Met Thr Asn Ser Thr Ala Ala Ser Arg Pro Pro Val Thr 85 90 95 ctg agg ctg gtg gtc cct gct agt cag tgt ggc tct ctc att gga aaa 810 Leu Arg Leu Val Val Pro Ala Ser Gln Cys Gly Ser Leu Ile Gly Lys 100 105 110 115 ggt gga tgc aag atc aag gaa ata cga gag agt aca ggg gct cag gtc 858 Gly Gly Cys Lys Ile Lys Glu Ile Arg Glu Ser Thr Gly Ala Gln Val 120 125 130 cag gtg gca ggg gat atg cta ccc aac tca act gag cgg gcc atc act 906 Gln Val Ala Gly Asp Met Leu Pro Asn Ser Thr Glu Arg Ala Ile Thr 135 140 145 att gct ggc att cca caa tcc atc att gag tgt gtc aaa cag atc tgc 954 Ile Ala Gly Ile Pro Gln Ser Ile Ile Glu Cys Val Lys Gln Ile Cys 150 155 160 gtg gtc atg ttg gag act ctc tcc cag tcc ccc ccg aag ggc gtg acc 1002 Val Val Met Leu Glu Thr Leu Ser Gln Ser Pro Pro Lys Gly Val Thr 165 170 175 atc ccg tac cgg ccc aag ccg tcc agc tct ccg gtc atc ttt gca ggt 1050 Ile Pro Tyr Arg Pro Lys Pro Ser Ser Ser Pro Val Ile Phe Ala Gly 180 185 190 195 ggt cag gac agg tac agc aca ggc agc gac agt gcg agc ttt ccc cac 1098 Gly Gln Asp Arg Tyr Ser Thr Gly Ser Asp Ser Ala Ser Phe Pro His 200 205 210 acc acc ccg tcc atg tgc ctc aac cct gac ctg gag gga cca cct cta 1146 Thr Thr Pro Ser Met Cys Leu Asn Pro Asp Leu Glu Gly Pro Pro Leu 215 220 225 gag gcc tat acc att caa gga cag tat gcc att cca cag cca gat ttg 1194 Glu Ala Tyr Thr Ile Gln Gly Gln Tyr Ala Ile Pro Gln Pro Asp Leu 230 235 240 acc aag ctg cac cag ttg gca atg caa cag tct cat ttt ccc atg acg 1242 Thr Lys Leu His Gln Leu Ala Met Gln Gln Ser His Phe Pro Met Thr 245 250 255 cat ggc aac acc gga ttc agt ggc att gaa tcc agc tct cca gag gtg 1290 His Gly Asn Thr Gly Phe Ser Gly Ile Glu Ser Ser Ser Pro Glu Val 260 265 270 275 aaa ggc tat tgg gca ggt ttg gat gca tct gct cag act act tct cat 1338 Lys Gly Tyr Trp Ala Gly Leu Asp Ala Ser Ala Gln Thr Thr Ser His 280 285 290 gaa ctc acc att cca aac gat ttg att ggc tgc ata atc ggg cgt caa 1386 Glu Leu Thr Ile Pro Asn Asp Leu Ile Gly Cys Ile Ile Gly Arg Gln 295 300 305 ggc gcc aaa atc aat gag atc cgt cag atg tct ggg gcg cag atc aaa 1434 Gly Ala Lys Ile Asn Glu Ile Arg Gln Met Ser Gly Ala Gln Ile Lys 310 315 320 att gcg aac cca gtg gaa gga tct act gat agg cag gtt acc atc act 1482 Ile Ala Asn Pro Val Glu Gly Ser Thr Asp Arg Gln Val Thr Ile Thr 325 330 335 gga tct gct gcc agc att agc ctg gct caa tat cta atc aat gtc agg 1530 Gly Ser Ala Ala Ser Ile Ser Leu Ala Gln Tyr Leu Ile Asn Val Arg 340 345 350 355 ctt tcc tcg gag acg ggt ggc atg ggg agc agc tag aaca atgcagattc 1580 Leu Ser Ser Glu Thr Gly Gly Met Gly Ser Ser * 360 365 atccataatc cctttctgct gttcaccacc acccatgatc catctgtgta gtttctgaac 1640 agtcagcgat tccaggtttt aaatagtttg taaattttca gtttctacac actttatcat 1700 ccactcgtga ttttttaatt aaagcgtttt aattccttt 1739 13 1054 DNA Homo sapiens CDS (263)..(784) 13 atttggccct cgaggccaag aattcggcac gagcaaagtt gtcatgaata ctgacttggg 60 cgtgggaccc atccgagatg tgctggacca catctacagt gcgctgtatg tggagctggt 120 ggtgaagaat cccctgtgcc cgctgggcca aactgtgcaa agtgagctct ttcgctcccg 180 actggactcc tatgttcgct ctctgccctt cttctccgcc cgggctggct gaagcaacct 240 acctcaagtc tcaggagaat tc atg tct gcc tgg ggc cct tcc ggg aac ccg 292 Met Ser Ala Trp Gly Pro Ser Gly Asn Pro 1 5 10 agc cca agg agt ggg ggc ggc ccc gga gcg agg ctc aca ctc cct gcc 340 Ser Pro Arg Ser Gly Gly Gly Pro Gly Ala Arg Leu Thr Leu Pro Ala 15 20 25 ctg cag atg act gtc cac aac ctg tac ctg ttt gac cgg aat gga gtg 388 Leu Gln Met Thr Val His Asn Leu Tyr Leu Phe Asp Arg Asn Gly Val 30 35 40 tgt ctg cac tac agc gaa tgg cac cgc aag aag caa gca ggg att ccc 436 Cys Leu His Tyr Ser Glu Trp His Arg Lys Lys Gln Ala Gly Ile Pro 45 50 55 aag gag gag gag tat aag ctg atg tac ggg atg ctc ttc tct atc cgc 484 Lys Glu Glu Glu Tyr Lys Leu Met Tyr Gly Met Leu Phe Ser Ile Arg 60 65 70 tcg ttt gtc agc aag atg tcc ccg cta gac atg aag gat ggc ttc ctg 532 Ser Phe Val Ser Lys Met Ser Pro Leu Asp Met Lys Asp Gly Phe Leu 75 80 85 90 gcc ttc caa act agc cgt tac aaa ctc cat tac tac gag acg ccc act 580 Ala Phe Gln Thr Ser Arg Tyr Lys Leu His Tyr Tyr Glu Thr Pro Thr 95 100 105 ggg atc aaa gtt gtc atg aat act gac ttg ggc gtg gga ccc atc cga 628 Gly Ile Lys Val Val Met Asn Thr Asp Leu Gly Val Gly Pro Ile Arg 110 115 120 gat gtg ctg cac cac atc tac agt gcg ctg tat gtg gag ctg gtg gtg 676 Asp Val Leu His His Ile Tyr Ser Ala Leu Tyr Val Glu Leu Val Val 125 130 135 aag aat ccc ctg tgc ccg ctg ggc caa act gtg caa agt gag ctc ttt 724 Lys Asn Pro Leu Cys Pro Leu Gly Gln Thr Val Gln Ser Glu Leu Phe 140 145 150 cgc tcc cga ctg gac tcc tat gtt cgc tct ctg ccc ttc ttc tcc gcc 772 Arg Ser Arg Leu Asp Ser Tyr Val Arg Ser Leu Pro Phe Phe Ser Ala 155 160 165 170 cgg gct ggc tga agc aacctacctc aagtctcagg agaattcatg tctgcctggg 827 Arg Ala Gly * gcccttccga acctgtgcca actaagggcc cccactgtaa gcccccgcac ccccaccccc 887 tgcccagagc aacagcctaa aggcctgccc tgatgctctc ctcctaccag agtgaagccc 947 acagagtccc tccacctcca caccaggccc tctctccagt tttatcccct gcctaatgct 1007 gcgagaagca cagaataaac tttttgtcac tctcaaaaaa aaaaaaa 1054 14 709 DNA Homo sapiens CDS (85)..(531) 14 aaggatcctt aattaaatta atcccccccc cccgctctag cagctgccgc tgagccgccg 60 gacggacgct cgtcttcgcc cgcc atg gcc gag agc gac tgg gac acg gtg 111 Met Ala Glu Ser Asp Trp Asp Thr Val 1 5 acg gtg ctg cgc aag aag ggc cct acg gcc gcc cag gcc aaa tcc aag 159 Thr Val Leu Arg Lys Lys Gly Pro Thr Ala Ala Gln Ala Lys Ser Lys 10 15 20 25 cag gct atc tta gcg gca cag aga cga gga gaa gat gtg gag act tcc 207 Gln Ala Ile Leu Ala Ala Gln Arg Arg Gly Glu Asp Val Glu Thr Ser 30 35 40 aag aaa tgg gct gct ggc cag aac aaa caa cat tct att acc aag aac 255 Lys Lys Trp Ala Ala Gly Gln Asn Lys Gln His Ser Ile Thr Lys Asn 45 50 55 acg gcc aag ctg gac cgg gag aca gag gag ctg cac cat gac agg gtg 303 Thr Ala Lys Leu Asp Arg Glu Thr Glu Glu Leu His His Asp Arg Val 60 65 70 acc ctg gag gtg ggc aag gtg atc cag caa ggt cgg cag agc aag ggg 351 Thr Leu Glu Val Gly Lys Val Ile Gln Gln Gly Arg Gln Ser Lys Gly 75 80 85 ctt acg cag aag gac ctg gcc acg aaa atc aat gag aag cca cag gtg 399 Leu Thr Gln Lys Asp Leu Ala Thr Lys Ile Asn Glu Lys Pro Gln Val 90 95 100 105 atc gcg gac tat gag agc gga cgg gcc ata ccc aat aac cag gtg ctt 447 Ile Ala Asp Tyr Glu Ser Gly Arg Ala Ile Pro Asn Asn Gln Val Leu 110 115 120 ggc aaa atc gag cgg gcc att ggc ctc aag ctc cgg gga aag gac att 495 Gly Lys Ile Glu Arg Ala Ile Gly Leu Lys Leu Arg Gly Lys Asp Ile 125 130 135 gga aag ccc atc gag aag ggg cct agg gcg aaa tga acac aaagcctcga 545 Gly Lys Pro Ile Glu Lys Gly Pro Arg Ala Lys * 140 145 aatcagtgcg ctccagctga tctcgttccg ccggttcccc ttggccgcca gttccgttct 605 cctcacgggc cgaacggaac aaggggtcca gcttgcgggg gaccctcccc agcccattcc 665 tgctgtcaaa caaacaaaac cttgcaaagc gaaaaaaaaa aaaa 709 15 662 DNA Homo sapiens CDS (46)..(387) 15 atttggccct cgaggccaag aattcggcac gaggacgggg ctggc atg acc ccg 54 Met Thr Pro 1 ggg gtc ttc cat gcc agt ccg cct cag tcg cag agg gtc cct cgg caa 102 Gly Val Phe His Ala Ser Pro Pro Gln Ser Gln Arg Val Pro Arg Gln 5 10 15 gcg ccc tgt gag tgg gcc att cgg aac att gga cag aag ccc aaa gag 150 Ala Pro Cys Glu Trp Ala Ile Arg Asn Ile Gly Gln Lys Pro Lys Glu 20 25 30 35 cca aat tgt cac aat tgt gga acc cac att ggc ctg aga tcc aaa acg 198 Pro Asn Cys His Asn Cys Gly Thr His Ile Gly Leu Arg Ser Lys Thr 40 45 50 ctt cga ggc acc cca aat tac ctg ccc att cgt cag gac acc cac cca 246 Leu Arg Gly Thr Pro Asn Tyr Leu Pro Ile Arg Gln Asp Thr His Pro 55 60 65 ccc agt gtt ata ttc tgc ctc gcc gga gtg ggt gtt ccc ggg ggc act 294 Pro Ser Val Ile Phe Cys Leu Ala Gly Val Gly Val Pro Gly Gly Thr 70 75 80 tgc cga cca gcc cct tgc gtc ccc agg ttt gca gct ctc ccc tgg gcc 342 Cys Arg Pro Ala Pro Cys Val Pro Arg Phe Ala Ala Leu Pro Trp Ala 85 90 95 act aac cat cct ggc ccg ggc tgc ctg tct gac ctc cgt gcc tag tcg 390 Thr Asn His Pro Gly Pro Gly Cys Leu Ser Asp Leu Arg Ala * 100 105 110 tggctctcca tcttgtctcc tccccgtgtc cccaatgtct tcagtggggg gcccctcttg 450 ggtcccctcc tctgccatca cctgaagacc cccacgccaa acactgaatg tcacctgtgc 510 ctgccgcctc ggtccacctt gcggcccgtg tttgactcaa ctcagctcct ttaacgctaa 570 tatttccggc aaaatcccat gcttgggttt tgtctttaac cttgtaacgc ttgcaatccc 630 aataaagcat taaaagtcat gaaaaaaaaa aa 662 16 525 DNA Homo sapiens CDS (190)..(375) 16 taggcctatt taggtgacac tatagaacaa gtttgtacaa aaaagcaggc tggtaccggt 60 ccggaattcc cgggatatcg tcgacccacg cgtccgcagc ggccggctgt tggggtccac 120 cacgccttcc acctgcccca ctgcttcttc gcttctctct tggaaagtcc agtctctcct 180 cggcttgca atg gac ccc aac tgc tcc tgc gcc gct ggt gtc tcc tgc 228 Met Asp Pro Asn Cys Ser Cys Ala Ala Gly Val Ser Cys 1 5 10 acc tgc gct ggt tcc tgc aag tgc aaa gag tgc aaa tgc acc tcc tgc 276 Thr Cys Ala Gly Ser Cys Lys Cys Lys Glu Cys Lys Cys Thr Ser Cys 15 20 25 aag aag agc tgc tgc tcc tgc tgc ccc gtg ggc tgt agc aag tgt gcc 324 Lys Lys Ser Cys Cys Ser Cys Cys Pro Val Gly Cys Ser Lys Cys Ala 30 35 40 45 cag ggc tgt gtt tgc aaa ggg gcg tca gag aag tgc agc tgc tgc gac 372 Gln Gly Cys Val Cys Lys Gly Ala Ser Glu Lys Cys Ser Cys Cys Asp 50 55 60 tga tgcc aggacaacct ttctcccaga tgtaaacaga gagacatgta caaacctgga 429 * tttttttttt ataccacctt gacccatttg ctacattcct tttcctgtga aatatgtgag 489 tgataattaa acactttaga cctgaaaaaa aaaaaa 525 17 895 DNA Homo sapiens CDS (258)..(776) 17 atttggccct cgaggccaag aattcggcac gagggcggag gtgtctaccc cgccggtgat 60 ggcgttgaac gccactggct tcccggcctt ccgtccgctg cctccgtccg attctgcgtc 120 tgcttgctga ggaggcggat taggggggcg cggagtctct tcccttgagt gcataggtcc 180 cggttggtag agggtttgag tccgcatcgc cacagctgaa ggctgcgagg gactaagagc 240 agaatatatc tttagaa atg agt tgc aca att gag aag gca ctt gcc gac 290 Met Ser Cys Thr Ile Glu Lys Ala Leu Ala Asp 1 5 10 gct aaa gct ctt gtt gaa aga tta aga gat cat gac gat gca gca gaa 338 Ala Lys Ala Leu Val Glu Arg Leu Arg Asp His Asp Asp Ala Ala Glu 15 20 25 tct ctg att gag caa acc aca gct ctc aac aag cga gta gaa gcc atg 386 Ser Leu Ile Glu Gln Thr Thr Ala Leu Asn Lys Arg Val Glu Ala Met 30 35 40 aaa cag tat cag gaa gaa att caa gaa ctt aat gaa gtc gcg aga cat 434 Lys Gln Tyr Gln Glu Glu Ile Gln Glu Leu Asn Glu Val Ala Arg His 45 50 55 cgg cca cgg tcc acg tta gtt atg gga atc cag caa gaa aac aga caa 482 Arg Pro Arg Ser Thr Leu Val Met Gly Ile Gln Gln Glu Asn Arg Gln 60 65 70 75 atc aga gag ttg caa caa gaa aac aaa gaa tta cgt aca tct ctg gaa 530 Ile Arg Glu Leu Gln Gln Glu Asn Lys Glu Leu Arg Thr Ser Leu Glu 80 85 90 gaa cat cag tcg gcc ttg gaa ctt ata atg agc aag tac cga gaa caa 578 Glu His Gln Ser Ala Leu Glu Leu Ile Met Ser Lys Tyr Arg Glu Gln 95 100 105 atg ttt aga ttg cta atg gct agc aaa aaa gat gat ccg ggt ata ata 626 Met Phe Arg Leu Leu Met Ala Ser Lys Lys Asp Asp Pro Gly Ile Ile 110 115 120 atg aag tta aaa gag cag cac tcc aag att gac atg gta cat cgt aac 674 Met Lys Leu Lys Glu Gln His Ser Lys Ile Asp Met Val His Arg Asn 125 130 135 aag tcc gaa gga ttc ttc ctt gat gca tct cga cac atc ctt gaa gca 722 Lys Ser Glu Gly Phe Phe Leu Asp Ala Ser Arg His Ile Leu Glu Ala 140 145 150 155 cct caa cat gga ctg gag aga agg cac ttg gaa gca aat cag aat gta 770 Pro Gln His Gly Leu Glu Arg Arg His Leu Glu Ala Asn Gln Asn Val 160 165 170 cac taa ataaacagtc aacttttggg gtgtggatgg aaggggggtc cattttaaaa 826 His * gtgcttttac attgaatttc cctcccagat tagatcagca aataaatgaa atttattaaa 886 aaaaaaaaa 895 18 1314 DNA Homo sapiens CDS (223)..(1254) 18 taagcttgcg gccgcccgcg agcggggcgg tgccacgtac ggctccggaa gaagcgacgg 60 aatctgctag ggcacaagag agacgggcgc tcgggctctc gcagtcctct tccgtcagtg 120 tcttttgctt cgactcccgg cggagcgcgc aacgtggagt gacgtgcagg ggccaagtgc 180 aacccaggca gccacggctg tttcggagct caggactcta aa atg gca gag cag 234 Met Ala Glu Gln 1 ctt tct cca gga aag gcg gtg gat cag gtg tgc acc ttc ctt ttc aaa 282 Leu Ser Pro Gly Lys Ala Val Asp Gln Val Cys Thr Phe Leu Phe Lys 5 10 15 20 aag cct ggg cgg aaa ggg gct gct gga cgc aga aag cgc ccg gcc tgc 330 Lys Pro Gly Arg Lys Gly Ala Ala Gly Arg Arg Lys Arg Pro Ala Cys 25 30 35 gac cca gag ccc gga gaa agc ggc agc agt agc gac gaa ggc tgc act 378 Asp Pro Glu Pro Gly Glu Ser Gly Ser Ser Ser Asp Glu Gly Cys Thr 40 45 50 gtg gtt cga ccg gaa aag aag cgg gtg acc cac aat cca atg ata cag 426 Val Val Arg Pro Glu Lys Lys Arg Val Thr His Asn Pro Met Ile Gln 55 60 65 aag acc cgt gac agt ggt aaa cag aag gcg gct tac ggc gac ttg agc 474 Lys Thr Arg Asp Ser Gly Lys Gln Lys Ala Ala Tyr Gly Asp Leu Ser 70 75 80 agc gaa gag gaa gag gaa aat gag ccc gag agt ctc ggc gtg gtt tat 522 Ser Glu Glu Glu Glu Glu Asn Glu Pro Glu Ser Leu Gly Val Val Tyr 85 90 95 100 aaa tcc acc cgt tcg gcg aaa ccc gtg gga cca gag gat atg gga gcg 570 Lys Ser Thr Arg Ser Ala Lys Pro Val Gly Pro Glu Asp Met Gly Ala 105 110 115 aca gct gtc tat gag ctg gac aca gag aaa gag cgc gat gca caa gcc 618 Thr Ala Val Tyr Glu Leu Asp Thr Glu Lys Glu Arg Asp Ala Gln Ala 120 125 130 atc ttt gag cgc agc cag aag atc cag gag gag ctg agg ggc aag gag 666 Ile Phe Glu Arg Ser Gln Lys Ile Gln Glu Glu Leu Arg Gly Lys Glu 135 140 145 gat gac aag atc tat cgg gga atc aac aat tat cag aaa tac atg aag 714 Asp Asp Lys Ile Tyr Arg Gly Ile Asn Asn Tyr Gln Lys Tyr Met Lys 150 155 160 ccc aag gat acg tct atg ggc aat gcc tct tcc ggg atg gtg agg aag 762 Pro Lys Asp Thr Ser Met Gly Asn Ala Ser Ser Gly Met Val Arg Lys 165 170 175 180 ggc ccc atc cga gcg ccc gag cat cta cgt gcc acc gtg cgc tgg gat 810 Gly Pro Ile Arg Ala Pro Glu His Leu Arg Ala Thr Val Arg Trp Asp 185 190 195 tac cag ccc gac atc tgt aag gac tac aaa gag act ggc ttc tgc ggc 858 Tyr Gln Pro Asp Ile Cys Lys Asp Tyr Lys Glu Thr Gly Phe Cys Gly 200 205 210 ttc gga gac agc tgc aaa ttc ctc cat gac cgt tca gat tac aag cat 906 Phe Gly Asp Ser Cys Lys Phe Leu His Asp Arg Ser Asp Tyr Lys His 215 220 225 ggg tgg cag atc gaa cgt gag ctt gat gag ggt cgc tat ggt gtc tat 954 Gly Trp Gln Ile Glu Arg Glu Leu Asp Glu Gly Arg Tyr Gly Val Tyr 230 235 240 gag gat gaa aac tat gaa gtg gga agc gat gat gag gaa ata cca ttc 1002 Glu Asp Glu Asn Tyr Glu Val Gly Ser Asp Asp Glu Glu Ile Pro Phe 245 250 255 260 aag tgt ttc atc tgt cgc cag agc ttc caa aac cca gtt gtc acc aag 1050 Lys Cys Phe Ile Cys Arg Gln Ser Phe Gln Asn Pro Val Val Thr Lys 265 270 275 tgc agg cat tat ttc tgc gag agc tgt gca ctg cag cat ttc cgc acc 1098 Cys Arg His Tyr Phe Cys Glu Ser Cys Ala Leu Gln His Phe Arg Thr 280 285 290 acc ccg cgc tgc tat gtc tgt gac cag cag acc aat ggc gtc ttc aat 1146 Thr Pro Arg Cys Tyr Val Cys Asp Gln Gln Thr Asn Gly Val Phe Asn 295 300 305 cca gcg aaa gaa ttg att gct aaa cta gag aag cat cga gct aca gga 1194 Pro Ala Lys Glu Leu Ile Ala Lys Leu Glu Lys His Arg Ala Thr Gly 310 315 320 gag ggt ggt gct tcc gac ttg cca gaa gac ccc gat gag gat gca att 1242 Glu Gly Gly Ala Ser Asp Leu Pro Glu Asp Pro Asp Glu Asp Ala Ile 325 330 335 340 ccc att act tag gtt tcccataatt cttaaattta aaaaataaac gttttgttct 1297 Pro Ile Thr * tttggaaaaa aaaaaaa 1314 19 1631 DNA Homo sapiens CDS (71)..(1459) 19 cctttgaagc ctgcggtacc ggtccggaat tcccgggtcg acccacgcgt ccgggcctct 60 gcagctcagc atg gct agg gta ctg gga gca ccc gtt gca ctg ggg ttg 109 Met Ala Arg Val Leu Gly Ala Pro Val Ala Leu Gly Leu 1 5 10 tgg agc cta tgc tgg tct ctg gcc att gcc acc cct ctt cct ccg act 157 Trp Ser Leu Cys Trp Ser Leu Ala Ile Ala Thr Pro Leu Pro Pro Thr 15 20 25 agt gcc cat ggg aat gtt gct gaa ggc gag acc aag cca gac cca gac 205 Ser Ala His Gly Asn Val Ala Glu Gly Glu Thr Lys Pro Asp Pro Asp 30 35 40 45 gtg act gaa cgc tgc tca gat ggc tgg agc ttt gat gct acc acc ctg 253 Val Thr Glu Arg Cys Ser Asp Gly Trp Ser Phe Asp Ala Thr Thr Leu 50 55 60 gat gac aat gga acc atg ctg ttt ttt aaa ggg gag ttt gtg tgg aag 301 Asp Asp Asn Gly Thr Met Leu Phe Phe Lys Gly Glu Phe Val Trp Lys 65 70 75 agt cac aaa tgg gac cgg gag tta atc tca gag aga tgg aag aat ttc 349 Ser His Lys Trp Asp Arg Glu Leu Ile Ser Glu Arg Trp Lys Asn Phe 80 85 90 ccc agc cct gtg gat gct gca ttc cgt caa ggt cac aac agt gtc ttt 397 Pro Ser Pro Val Asp Ala Ala Phe Arg Gln Gly His Asn Ser Val Phe 95 100 105 ctg atc aag ggg gac aaa gtc tgg gta tac cct cct gaa aag aag gag 445 Leu Ile Lys Gly Asp Lys Val Trp Val Tyr Pro Pro Glu Lys Lys Glu 110 115 120 125 aaa gga tac cca aag ttg ctc caa gat gaa ttt cct gga atc cca tcc 493 Lys Gly Tyr Pro Lys Leu Leu Gln Asp Glu Phe Pro Gly Ile Pro Ser 130 135 140 cca ctg gat gca gct gtg gaa tgt cac cgt gga gaa tgt caa gct gaa 541 Pro Leu Asp Ala Ala Val Glu Cys His Arg Gly Glu Cys Gln Ala Glu 145 150 155 ggc gtc ctc ttc ttc caa ggt gac cgc gag tgg ttc tgg gac ttg gct 589 Gly Val Leu Phe Phe Gln Gly Asp Arg Glu Trp Phe Trp Asp Leu Ala 160 165 170 acg gga acc atg aag gag cgt tcc tgg cca gct gtt ggg aac tgc tcc 637 Thr Gly Thr Met Lys Glu Arg Ser Trp Pro Ala Val Gly Asn Cys Ser 175 180 185 tct gcc ctg aga tgg ctg ggc cgc tac tac tgc ttc cag ggt aac caa 685 Ser Ala Leu Arg Trp Leu Gly Arg Tyr Tyr Cys Phe Gln Gly Asn Gln 190 195 200 205 ttc ctg cgc ttc gac cct gtc agg gga gag gtg cct ccc agg tac ccg 733 Phe Leu Arg Phe Asp Pro Val Arg Gly Glu Val Pro Pro Arg Tyr Pro 210 215 220 cgg gat gtc cga gac tac ttc atg ccc tgc cct ggc aga ggc cat gga 781 Arg Asp Val Arg Asp Tyr Phe Met Pro Cys Pro Gly Arg Gly His Gly 225 230 235 cac agg aat ggg act ggc cat ggg aac agt acc cac cat ggc cct gag 829 His Arg Asn Gly Thr Gly His Gly Asn Ser Thr His His Gly Pro Glu 240 245 250 tat atg cgc tgt agc cca cat cta gtc ttg tct gca ctg acg tct gac 877 Tyr Met Arg Cys Ser Pro His Leu Val Leu Ser Ala Leu Thr Ser Asp 255 260 265 aac cat ggt gcc acc tat gcc ttc agt ggg acc cac tac tgg cgt ctg 925 Asn His Gly Ala Thr Tyr Ala Phe Ser Gly Thr His Tyr Trp Arg Leu 270 275 280 285 gac acc agc cgg gat ggc tgg cat agc tgg ccc att gct cat cag tgg 973 Asp Thr Ser Arg Asp Gly Trp His Ser Trp Pro Ile Ala His Gln Trp 290 295 300 ccc cag ggt cct tca gca gtg gat gct gcc ttt tcc tgg gaa gaa aaa 1021 Pro Gln Gly Pro Ser Ala Val Asp Ala Ala Phe Ser Trp Glu Glu Lys 305 310 315 ctc tat ctg gtc cag ggc acc cag gta tat gtc ttc ctg aca aag gga 1069 Leu Tyr Leu Val Gln Gly Thr Gln Val Tyr Val Phe Leu Thr Lys Gly 320 325 330 ggc tat acc cta gta agc ggt tat ccg aag cgg ctg gag aag gaa gtc 1117 Gly Tyr Thr Leu Val Ser Gly Tyr Pro Lys Arg Leu Glu Lys Glu Val 335 340 345 ggg acc cct cat ggg att atc ctg gac tct gtg gat gcg gcc ttt atc 1165 Gly Thr Pro His Gly Ile Ile Leu Asp Ser Val Asp Ala Ala Phe Ile 350 355 360 365 tgc cct ggg tct tct cgg ctc cat atc atg gca gga cgg cgg ctg tgg 1213 Cys Pro Gly Ser Ser Arg Leu His Ile Met Ala Gly Arg Arg Leu Trp 370 375 380 tgg ctg gac ctg aag tca gga gcc caa gcc acg tgg aca gag ctt cct 1261 Trp Leu Asp Leu Lys Ser Gly Ala Gln Ala Thr Trp Thr Glu Leu Pro 385 390 395 tgg ccc cat gag aag gta gac gga gcc ttg tgt atg gaa aag tcc ctt 1309 Trp Pro His Glu Lys Val Asp Gly Ala Leu Cys Met Glu Lys Ser Leu 400 405 410 ggc cct aac tca tgt tcc gcc aat ggt ccc ggc ttg tac ctc atc cat 1357 Gly Pro Asn Ser Cys Ser Ala Asn Gly Pro Gly Leu Tyr Leu Ile His 415 420 425 ggt ccc aat ttg tac tgc tac agt gat gtg gag aaa ctg aat gca gcc 1405 Gly Pro Asn Leu Tyr Cys Tyr Ser Asp Val Glu Lys Leu Asn Ala Ala 430 435 440 445 aag gcc ctt ccg caa ccc cag aat gtg acc agt ctc ctg ggc tgc act 1453 Lys Ala Leu Pro Gln Pro Gln Asn Val Thr Ser Leu Leu Gly Cys Thr 450 455 460 cac tga ggggccttct gacatgagtc tggcctggcc ccacctccta gttcctcata 1509 His * ataaagacag attgcttctt cgcttctcac tgaggggcct tctgacatga gtctggcctg 1569 gccccacctc cccagtttct cataataaag acagattgct tcttcacttg aaaaaaaaaa 1629 aa 1631 20 1764 DNA Homo sapiens CDS (203)..(1045) 20 gatttgctct gccagcagct gtcggtgccg cgctcgacac cgagtcctag ctaggcgctc 60 acagaatacg cgctccctcc ctcccccttc tctgtccccc gcctctcgct caccccggcc 120 cactccagcg gcgactttga gggattccct ctctggcggc ctctgcagca gcacagccgg 180 cctcattcgg ggcactgcga gt atg gat ctc caa gga aga ggg gtc ccc agc 232 Met Asp Leu Gln Gly Arg Gly Val Pro Ser 1 5 10 atc gac aga ctt cga gtt ctc ctg atg ttg ttc cat aca atg gct caa 280 Ile Asp Arg Leu Arg Val Leu Leu Met Leu Phe His Thr Met Ala Gln 15 20 25 atc atg gca gaa caa gaa gtg gaa aat ctc tca ggc ctt tcc act aac 328 Ile Met Ala Glu Gln Glu Val Glu Asn Leu Ser Gly Leu Ser Thr Asn 30 35 40 cct gaa aaa gat ata ttt gtg gtg cgg gaa aat ggg acg acg tgt ctc 376 Pro Glu Lys Asp Ile Phe Val Val Arg Glu Asn Gly Thr Thr Cys Leu 45 50 55 atg gca gag ttt gca gcc aaa ttt att gta cct tat gat gtg tgg gcc 424 Met Ala Glu Phe Ala Ala Lys Phe Ile Val Pro Tyr Asp Val Trp Ala 60 65 70 agc aac tac gta gat ctg atc aca gaa cag gcc gat atc gca ttg acc 472 Ser Asn Tyr Val Asp Leu Ile Thr Glu Gln Ala Asp Ile Ala Leu Thr 75 80 85 90 cgg gga gct gag gtg aag ggc cgc tgt ggc cac agc cag tcg gag ctg 520 Arg Gly Ala Glu Val Lys Gly Arg Cys Gly His Ser Gln Ser Glu Leu 95 100 105 caa gtg ttc tgg gtg gat cgc gca tat gca ctc aaa atg ctc ttt gta 568 Gln Val Phe Trp Val Asp Arg Ala Tyr Ala Leu Lys Met Leu Phe Val 110 115 120 aag gaa agc cac aac atg tcc aag gga cct gag gcg act tgg agg ctg 616 Lys Glu Ser His Asn Met Ser Lys Gly Pro Glu Ala Thr Trp Arg Leu 125 130 135 agc aaa gtg cag ttt gtc tac gac tcc tcg gag aaa acc cac ttc aaa 664 Ser Lys Val Gln Phe Val Tyr Asp Ser Ser Glu Lys Thr His Phe Lys 140 145 150 gac gca gtc agt gct ggg aag cac aca gcc aac tcg cac cac ctc tct 712 Asp Ala Val Ser Ala Gly Lys His Thr Ala Asn Ser His His Leu Ser 155 160 165 170 gcc ttg gtc acc ccc gct ggg aag tcc tat gag tgt caa gct caa caa 760 Ala Leu Val Thr Pro Ala Gly Lys Ser Tyr Glu Cys Gln Ala Gln Gln 175 180 185 acc att tca ctg gcc tct agt gat ccg cag aag acg gtc acc atg atc 808 Thr Ile Ser Leu Ala Ser Ser Asp Pro Gln Lys Thr Val Thr Met Ile 190 195 200 ctg tct gcg gtc cac atc caa cct ttt gac att atc tca gat ttt gtc 856 Leu Ser Ala Val His Ile Gln Pro Phe Asp Ile Ile Ser Asp Phe Val 205 210 215 ttc agt gaa gag cat aaa tgc cca gtg gat gag cgg gag caa ctg gaa 904 Phe Ser Glu Glu His Lys Cys Pro Val Asp Glu Arg Glu Gln Leu Glu 220 225 230 gaa acc ttg ccc ctg att ttg ggg ctc atc ttg ggc ctc gtc atc atg 952 Glu Thr Leu Pro Leu Ile Leu Gly Leu Ile Leu Gly Leu Val Ile Met 235 240 245 250 gta aca ctc gcg att tac cac gtc cac cac aaa atg act gcc aac cag 1000 Val Thr Leu Ala Ile Tyr His Val His His Lys Met Thr Ala Asn Gln 255 260 265 gtg cag atc cct cgg gac aga tcc cag tat aag cac atg ggc tag agg 1048 Val Gln Ile Pro Arg Asp Arg Ser Gln Tyr Lys His Met Gly * 270 275 280 ccgttaggca ggcaccccct attcctgctc ccccaactgg atcaggtaga acaacaaaag 1108 cacttttcca tcttgtacac gagatacacc aacatagcta caatcaaaca ggcctgggta 1168 tctgaggctt gcttggcttg tgtccatgct taaacccacg gaagggggag actctttcgg 1228 atttgtaggg tgaaatggca attattctct ccatgctggg gaggagggga ggagggtctc 1288 agacagcttt cgtgctcatg gtggcttggc tttgactctc caaagagcaa taaatgccac 1348 ttggagctgt atctggcccc aaagtttagg gattgaaaac atgcttcttt gaggaggaaa 1408 cccctttagg ttcagaagaa tatggggtgc tttgctccct tggacacagc tggcttatcc 1468 tatacagttg tcaatgcaca cagaatacaa cctcatgctc cctgcagcaa gacccctgaa 1528 agtgattcat gcttctggct ggcattctgc atgtttagtg attgtcttgg gaatgtttca 1588 ctgctacccg catccagcga ctgcagcacc agaaaacgac taatgtaact atgcagagtt 1648 gtttggactt cttcctgtgc caggtccaag tcgggggacc tgaagaatca atctgtgtga 1708 gtctgttttt caaaatgaaa taaaacacac tattctctgg caaaaaaaaa aaaaaa 1764 21 1872 DNA Homo sapiens CDS (232)..(1716) 21 ttggacacta gtgcagaaat atgtcccgag agcaaaatag agaggccaca agtgacagaa 60 agattttaca catacatgtg cgagatacaa aaacagtgaa ggatgtacag aagccaaaaa 120 atgtgaacaa gacagctgaa aaagttagaa ttataaaata tttgttggga gagctcatgg 180 cccctggtag cagaacaaga gatttcagaa attcagaggt tgattacaga a atg gag 237 Met Glu 1 gca tgt ata tct gta ctt cca aca gta agt gga aac aca gat att caa 285 Ala Cys Ile Ser Val Leu Pro Thr Val Ser Gly Asn Thr Asp Ile Gln 5 10 15 gtt gag ata gca ctg gcc atg caa cca tta aga agt gag aat gct cag 333 Val Glu Ile Ala Leu Ala Met Gln Pro Leu Arg Ser Glu Asn Ala Gln 20 25 30 tta cga agg cag ttg aga att ttg aac cag caa ctc aga gaa caa cag 381 Leu Arg Arg Gln Leu Arg Ile Leu Asn Gln Gln Leu Arg Glu Gln Gln 35 40 45 50 aaa act caa aaa cca tct ggt gct gtg gat tgc aac ctt gaa ttg ttt 429 Lys Thr Gln Lys Pro Ser Gly Ala Val Asp Cys Asn Leu Glu Leu Phe 55 60 65 tct ctt cag tca ttg aat atg tca ctg caa aat caa ttg gag gag tca 477 Ser Leu Gln Ser Leu Asn Met Ser Leu Gln Asn Gln Leu Glu Glu Ser 70 75 80 cta aag agc cag gaa tta ctg cag agt aaa aat gaa gag ctg tta aaa 525 Leu Lys Ser Gln Glu Leu Leu Gln Ser Lys Asn Glu Glu Leu Leu Lys 85 90 95 gtg att gaa aat cag aaa gat gaa aac aaa aaa ttt agt agt ata ttt 573 Val Ile Glu Asn Gln Lys Asp Glu Asn Lys Lys Phe Ser Ser Ile Phe 100 105 110 aaa gac aaa gat caa act ata ctt gaa aat aaa cag caa tat gat att 621 Lys Asp Lys Asp Gln Thr Ile Leu Glu Asn Lys Gln Gln Tyr Asp Ile 115 120 125 130 gag ata aca aga ata aaa att gaa ttg gag gaa gcc cta gtc aat gtg 669 Glu Ile Thr Arg Ile Lys Ile Glu Leu Glu Glu Ala Leu Val Asn Val 135 140 145 aaa agc tcc cag ttt aag tta gaa act gct gaa aag gaa aac cag ata 717 Lys Ser Ser Gln Phe Lys Leu Glu Thr Ala Glu Lys Glu Asn Gln Ile 150 155 160 ttg ggg ata aca tta cgt cag cgt gat gct gag gtg act cga cta aga 765 Leu Gly Ile Thr Leu Arg Gln Arg Asp Ala Glu Val Thr Arg Leu Arg 165 170 175 gaa tta acc aga act tta cag act agc atg gca aag ctt ctc tcc gat 813 Glu Leu Thr Arg Thr Leu Gln Thr Ser Met Ala Lys Leu Leu Ser Asp 180 185 190 ctt agt gtg gac agt gct cgc tgc aag cct ggg aat aac ctt acc aaa 861 Leu Ser Val Asp Ser Ala Arg Cys Lys Pro Gly Asn Asn Leu Thr Lys 195 200 205 210 tca ctc ttg aac att cat gat aaa caa ctt caa cat gac cca gct cct 909 Ser Leu Leu Asn Ile His Asp Lys Gln Leu Gln His Asp Pro Ala Pro 215 220 225 gct cac act tcc ata atg agc tat cta aat aag tta gaa aca aat tac 957 Ala His Thr Ser Ile Met Ser Tyr Leu Asn Lys Leu Glu Thr Asn Tyr 230 235 240 agt ttt aca cat tca gag cca ctt tct aca att aaa aat gag gaa acc 1005 Ser Phe Thr His Ser Glu Pro Leu Ser Thr Ile Lys Asn Glu Glu Thr 245 250 255 ata gag cca gac aaa acc tat gaa aat gtt ctg tcc tcc aga ggc cct 1053 Ile Glu Pro Asp Lys Thr Tyr Glu Asn Val Leu Ser Ser Arg Gly Pro 260 265 270 caa aat agt aac act agg ggc atg gag gaa gca tct gca cct gga att 1101 Gln Asn Ser Asn Thr Arg Gly Met Glu Glu Ala Ser Ala Pro Gly Ile 275 280 285 290 att tct gcc ctt tca aaa cag gat tct gat gaa ggg agt gaa act atg 1149 Ile Ser Ala Leu Ser Lys Gln Asp Ser Asp Glu Gly Ser Glu Thr Met 295 300 305 gct tta ata gaa gat gag cat aat ttg gat aat aca att tac att cct 1197 Ala Leu Ile Glu Asp Glu His Asn Leu Asp Asn Thr Ile Tyr Ile Pro 310 315 320 ttt gct aga agc act cct gaa aag aaa tca cca ctt tct aag aga cta 1245 Phe Ala Arg Ser Thr Pro Glu Lys Lys Ser Pro Leu Ser Lys Arg Leu 325 330 335 tcc cct cag cca caa ata aga gca gct aca aca cag cta gtc agc aac 1293 Ser Pro Gln Pro Gln Ile Arg Ala Ala Thr Thr Gln Leu Val Ser Asn 340 345 350 agt gga ctt gct gtc tct gga aaa gaa aat aaa ctg tgt aca cct gta 1341 Ser Gly Leu Ala Val Ser Gly Lys Glu Asn Lys Leu Cys Thr Pro Val 355 360 365 370 atc tgt tcc tct tca aca aag gaa gca gaa gat gca cct gaa aaa ctt 1389 Ile Cys Ser Ser Ser Thr Lys Glu Ala Glu Asp Ala Pro Glu Lys Leu 375 380 385 tcc aga gca tct gat atg aag gac aca cag ctc ctc aag aaa ata aag 1437 Ser Arg Ala Ser Asp Met Lys Asp Thr Gln Leu Leu Lys Lys Ile Lys 390 395 400 gaa gca att ggt aag atc cct gct gcc acc aag gag cca gag gaa caa 1485 Glu Ala Ile Gly Lys Ile Pro Ala Ala Thr Lys Glu Pro Glu Glu Gln 405 410 415 act gca tgt cat ggc cca tca ggt tgt ctt agc aac agc ctt caa gtg 1533 Thr Ala Cys His Gly Pro Ser Gly Cys Leu Ser Asn Ser Leu Gln Val 420 425 430 aaa ggc aat act gtc tgt gat ggt agt gtt ttc act tct gac ttg atg 1581 Lys Gly Asn Thr Val Cys Asp Gly Ser Val Phe Thr Ser Asp Leu Met 435 440 445 450 tct gac tgg agc atc tct tcg ttt tca acg ttc act tct cgt gat gaa 1629 Ser Asp Trp Ser Ile Ser Ser Phe Ser Thr Phe Thr Ser Arg Asp Glu 455 460 465 caa gac ttc aga aat ggc ctt gcg gca tta gat gcc aac ata gct aga 1677 Gln Asp Phe Arg Asn Gly Leu Ala Ala Leu Asp Ala Asn Ile Ala Arg 470 475 480 ctc cag aag tct tta agg act ggt ctt ctg gag aaa tga attcagaaga 1726 Leu Gln Lys Ser Leu Arg Thr Gly Leu Leu Glu Lys * 485 490 495 aaattcatca ggtgcttctt tttaaaacta gaacttggct atattgaatg tgtatttttc 1786 tttagtgaaa tgatgtttta tgttattatg tgtgaagtaa tatattgtac aagtaataaa 1846 tgtattgttg agataaaaaa aaaaaa 1872 22 981 DNA Homo sapiens CDS (125)..(904) 22 atcgaaggat gatgtatata actatctatt cgatgatgaa gataccccac caaacccaaa 60 aaaagagatc tctcgaggat ccgaattcgc ggccgcgtcg acgagaggcc tggaggacac 120 caac atg aac aag ttg aaa tca tcg cag aag gat aaa gtt cgt cag ttt 169 Met Asn Lys Leu Lys Ser Ser Gln Lys Asp Lys Val Arg Gln Phe 1 5 10 15 atg atc ttc aca caa tct agt gaa aaa aca gca gta agt tgt ctt tct 217 Met Ile Phe Thr Gln Ser Ser Glu Lys Thr Ala Val Ser Cys Leu Ser 20 25 30 caa aat gac tgg aag tta gat gtt gca aca gat aat ttt ttc caa aat 265 Gln Asn Asp Trp Lys Leu Asp Val Ala Thr Asp Asn Phe Phe Gln Asn 35 40 45 cct gaa ctt tat ata cga gag agt gta aaa gga tca ttg gac agg aag 313 Pro Glu Leu Tyr Ile Arg Glu Ser Val Lys Gly Ser Leu Asp Arg Lys 50 55 60 aag tta gaa cag ctg tac aat aga tac aaa gac cct caa gat gag aat 361 Lys Leu Glu Gln Leu Tyr Asn Arg Tyr Lys Asp Pro Gln Asp Glu Asn 65 70 75 aaa att gga ata gat ggc ata cag cag ttc tgt gat gac ctg gca ctc 409 Lys Ile Gly Ile Asp Gly Ile Gln Gln Phe Cys Asp Asp Leu Ala Leu 80 85 90 95 gat cca gcc agc att agt gtg ttg att att gca tgg aag ttc aga gca 457 Asp Pro Ala Ser Ile Ser Val Leu Ile Ile Ala Trp Lys Phe Arg Ala 100 105 110 gca aca cag tgc gag ttc tcc aaa cag gag ttc atg gat ggc atg aca 505 Ala Thr Gln Cys Glu Phe Ser Lys Gln Glu Phe Met Asp Gly Met Thr 115 120 125 gaa tta gga tgt gac agc ata gaa aaa cta aag gcc cag ata ccc aag 553 Glu Leu Gly Cys Asp Ser Ile Glu Lys Leu Lys Ala Gln Ile Pro Lys 130 135 140 atg gaa caa gaa ttg aaa gaa cca gga cga ttt aag gat ttt tac cag 601 Met Glu Gln Glu Leu Lys Glu Pro Gly Arg Phe Lys Asp Phe Tyr Gln 145 150 155 ttt act ttt aat ttt gca aag aat cca gga caa aaa gga tta gat cta 649 Phe Thr Phe Asn Phe Ala Lys Asn Pro Gly Gln Lys Gly Leu Asp Leu 160 165 170 175 gaa atg gcc att gcc tac tgg aac tta gtg ctt aat gga aga ttt aaa 697 Glu Met Ala Ile Ala Tyr Trp Asn Leu Val Leu Asn Gly Arg Phe Lys 180 185 190 ttc tta gac tta tgg aat aaa ttt ttg ttg gaa cat cat aaa cga tca 745 Phe Leu Asp Leu Trp Asn Lys Phe Leu Leu Glu His His Lys Arg Ser 195 200 205 ata cca aaa gac act tgg aat ctt ctt tta gac ttc agt acg atg att 793 Ile Pro Lys Asp Thr Trp Asn Leu Leu Leu Asp Phe Ser Thr Met Ile 210 215 220 gca gat gac atg tct aat tat gat gaa gaa gga gca tgg cct gtt ctt 841 Ala Asp Asp Met Ser Asn Tyr Asp Glu Glu Gly Ala Trp Pro Val Leu 225 230 235 att gat gac ttt gtg gaa ttt gca cgc cct caa att gct ggg aca aaa 889 Ile Asp Asp Phe Val Glu Phe Ala Arg Pro Gln Ile Ala Gly Thr Lys 240 245 250 255 agt aca aca gtg tag cactaaagga accttctaga atgtacatag tctgtacaat 944 Ser Thr Thr Val * 260 aaatacaaca gaaaattgca cagtcaaaaa aaaaaaa 981 23 1028 DNA Homo sapiens CDS (336)..(917) 23 ccggaattcc cgggtcgacc cacgcgtccg aaagaggcct gcaatccctc ggcgcggggc 60 aggttccggg ctgcttaggt tggcaccggt ccgtggtccc cgggggcgca gtcgcagcgc 120 tcccgccctc caggcgtcag cgagtgcgcg gtccagtgcg gccggaacct ggcgcaactc 180 ctagagcggt ccttggggag acgcgggtcc cagtcctgcg gctcctactg gggagtgcgc 240 tggtcggaag attgctggac tcgctgaaga gagactacgc aggaaagccc cagccaccca 300 tcaaatcaga gagaaggaat ccaccttctt acgct atg gca ggt aag aaa gta 353 Met Ala Gly Lys Lys Val 1 5 ctc att gtc tat gca cac cag gaa ccc aag tct ttc aac gga tcc ttg 401 Leu Ile Val Tyr Ala His Gln Glu Pro Lys Ser Phe Asn Gly Ser Leu 10 15 20 aag aat gtg gct gta gat gaa ctg agc agg cag ggc tgc acc gtc aca 449 Lys Asn Val Ala Val Asp Glu Leu Ser Arg Gln Gly Cys Thr Val Thr 25 30 35 gtg tct gat ttg tat gcc atg aac ctt gag ccg agg gcc aca gac aaa 497 Val Ser Asp Leu Tyr Ala Met Asn Leu Glu Pro Arg Ala Thr Asp Lys 40 45 50 gat atc act ggt act ctt tct aat cct gag gtt ttc aat tat gga gtg 545 Asp Ile Thr Gly Thr Leu Ser Asn Pro Glu Val Phe Asn Tyr Gly Val 55 60 65 70 gaa acc cac gaa gcc tac aag caa agg tct ctg gct agc gac atc act 593 Glu Thr His Glu Ala Tyr Lys Gln Arg Ser Leu Ala Ser Asp Ile Thr 75 80 85 gat gag cag aaa aag gtt cgg gag gct gac cta gtg ata ttt cag ggt 641 Asp Glu Gln Lys Lys Val Arg Glu Ala Asp Leu Val Ile Phe Gln Gly 90 95 100 aaa cta gcg ctc ctt tcc gta acc acg gga ggc acg gcc gag atg tac 689 Lys Leu Ala Leu Leu Ser Val Thr Thr Gly Gly Thr Ala Glu Met Tyr 105 110 115 acg aag aca gga gtc aat gga gat tct cga tac ttc ctg tgg cca ctc 737 Thr Lys Thr Gly Val Asn Gly Asp Ser Arg Tyr Phe Leu Trp Pro Leu 120 125 130 cag cat ggc aca tta cac ttc tgt gga ttt aaa gtc ctt gcc cct cag 785 Gln His Gly Thr Leu His Phe Cys Gly Phe Lys Val Leu Ala Pro Gln 135 140 145 150 atc agc ttt gct cct gaa att gca tcc gaa gaa gaa aga aag ggg atg 833 Ile Ser Phe Ala Pro Glu Ile Ala Ser Glu Glu Glu Arg Lys Gly Met 155 160 165 gtg gct gcg tgg tcc cag agg ctg cag acc atc tgg aag gaa gag ccc 881 Val Ala Ala Trp Ser Gln Arg Leu Gln Thr Ile Trp Lys Glu Glu Pro 170 175 180 atc ccc tgc aca gcc cac tgg cac ttc ggg caa taa ctct gtggcacgtg 931 Ile Pro Cys Thr Ala His Trp His Phe Gly Gln * 185 190 ggcatcacgt aagcagcaca ctaggaggcc caggcgcagg caaagagaag atggtgctgt 991 catgaaataa aattacaaca tagctaaaaa aaaaaaa 1028 24 2136 DNA Homo sapiens CDS (551)..(1729) 24 ctaatcttca taggatcact atagggaatt tggccctcga gcaagaattc ggcacgaggc 60 cgaacctggc ttcgctaacg ccctcccagc tccctcgggc ctgacttccg gtttcctcgc 120 gcgtccctgg cgccgagccc gcggacagcg gcagcccctt ttccggctga gagctcatcc 180 acacttccaa tcactttccg gagtgcttcc cctccctccg gcccgtgctg gtcccgacgg 240 cgggcctggg tctcgcgcgc gtattgctgg gtaacgggcc ttctcccgcg tcggcccggc 300 ccctcctgcc tcggctcgtc cctccttcca gaacgtcccg ggctcctgcc gagtcagaag 360 aaatgggact ccctccgcga cgtgcccgga gcagctccct tcgctgtgga agcggcggtg 420 tcttcgaaga aaccggaagc ccgtggtgac ccctggcgac ccggtttgtt ttcggtccgt 480 ttccaaacac taaggaatcg aaactcggcg gccttggggg cggccctacg tagcctggct 540 tctggttgtc atg gat gca ctg gta gaa gat gat atc tgt att ctg aat 589 Met Asp Ala Leu Val Glu Asp Asp Ile Cys Ile Leu Asn 1 5 10 cat gaa aaa gcc cat aag aga gat aca gtg act cca gtt tca ata tat 637 His Glu Lys Ala His Lys Arg Asp Thr Val Thr Pro Val Ser Ile Tyr 15 20 25 tca gga gat gaa tct gtt gct tcc cat ttt gct ctt gtc act gca tat 685 Ser Gly Asp Glu Ser Val Ala Ser His Phe Ala Leu Val Thr Ala Tyr 30 35 40 45 gaa gac atc aaa aaa cga ctt aag gat tca gag aaa gag aac tct ttg 733 Glu Asp Ile Lys Lys Arg Leu Lys Asp Ser Glu Lys Glu Asn Ser Leu 50 55 60 tta aag aag aga ata aga ttt ttg gaa gaa aag cta ata gct cga ttt 781 Leu Lys Lys Arg Ile Arg Phe Leu Glu Glu Lys Leu Ile Ala Arg Phe 65 70 75 gaa gaa gaa aca agt tcc gtg gga cga gaa caa gta aat aag gcc tat 829 Glu Glu Glu Thr Ser Ser Val Gly Arg Glu Gln Val Asn Lys Ala Tyr 80 85 90 cat gca tat cga gag gtt tgc att gat aga gat aat ttg aag agc aaa 877 His Ala Tyr Arg Glu Val Cys Ile Asp Arg Asp Asn Leu Lys Ser Lys 95 100 105 ctg gac aaa atg aat aaa gac aac tct gaa tct ttg aaa gta ttg aat 925 Leu Asp Lys Met Asn Lys Asp Asn Ser Glu Ser Leu Lys Val Leu Asn 110 115 120 125 gag cag cta caa tct aaa gaa gta gaa ctc ctc cag ctg agg aca gag 973 Glu Gln Leu Gln Ser Lys Glu Val Glu Leu Leu Gln Leu Arg Thr Glu 130 135 140 gtg gaa act cag cag gtg atg agg aat tta aat cca cct tca tca aac 1021 Val Glu Thr Gln Gln Val Met Arg Asn Leu Asn Pro Pro Ser Ser Asn 145 150 155 tgg gag gtg gaa aag ttg agc tgt gac ctg aag atc cat ggt ttg gaa 1069 Trp Glu Val Glu Lys Leu Ser Cys Asp Leu Lys Ile His Gly Leu Glu 160 165 170 caa gag ctg gaa ctg atg agg aaa gaa tgt agc gat ctc aaa ata gaa 1117 Gln Glu Leu Glu Leu Met Arg Lys Glu Cys Ser Asp Leu Lys Ile Glu 175 180 185 cta cag aaa gcc aaa caa acg gat cca tat cag gaa gac aat ctg aag 1165 Leu Gln Lys Ala Lys Gln Thr Asp Pro Tyr Gln Glu Asp Asn Leu Lys 190 195 200 205 agc aga gat ctc caa aaa cta agc att tca agt gat aat atg cag cat 1213 Ser Arg Asp Leu Gln Lys Leu Ser Ile Ser Ser Asp Asn Met Gln His 210 215 220 gca tac tgg gaa ctg aag aga gaa atg tct aat tta cat ctg gtg act 1261 Ala Tyr Trp Glu Leu Lys Arg Glu Met Ser Asn Leu His Leu Val Thr 225 230 235 caa gta caa gct gaa cta cta aga aaa ctg aaa acc tca act gca atc 1309 Gln Val Gln Ala Glu Leu Leu Arg Lys Leu Lys Thr Ser Thr Ala Ile 240 245 250 aag aaa gcc tgt gcc cct gta gga tgc agt gaa gac ctt gga aga gac 1357 Lys Lys Ala Cys Ala Pro Val Gly Cys Ser Glu Asp Leu Gly Arg Asp 255 260 265 agc aca aaa ctg cac ttg atg aat ttt act gca aca tac aca aga cat 1405 Ser Thr Lys Leu His Leu Met Asn Phe Thr Ala Thr Tyr Thr Arg His 270 275 280 285 ccc cct ctc tta cca aat ggc aaa gct ctt tgt cat acc aca tct tcc 1453 Pro Pro Leu Leu Pro Asn Gly Lys Ala Leu Cys His Thr Thr Ser Ser 290 295 300 cct tta cca gga gat gta aag gtt tta tca gag aaa gca atc ctc caa 1501 Pro Leu Pro Gly Asp Val Lys Val Leu Ser Glu Lys Ala Ile Leu Gln 305 310 315 tca tgg aca gac aat gag aga tcc att cct aat gat ggt aca tgc ttt 1549 Ser Trp Thr Asp Asn Glu Arg Ser Ile Pro Asn Asp Gly Thr Cys Phe 320 325 330 cag gaa cac agt tct tat ggc aga aat tct ctg gaa gac aat tcc tgg 1597 Gln Glu His Ser Ser Tyr Gly Arg Asn Ser Leu Glu Asp Asn Ser Trp 335 340 345 gta ttt cca agt cct cct aaa tca agt gag aca gca ttt ggg gaa act 1645 Val Phe Pro Ser Pro Pro Lys Ser Ser Glu Thr Ala Phe Gly Glu Thr 350 355 360 365 aaa act aaa act ttg cct tta ccc aac ctt cca cca ctg cat tac ttg 1693 Lys Thr Lys Thr Leu Pro Leu Pro Asn Leu Pro Pro Leu His Tyr Leu 370 375 380 gat caa cat aat cag aac tgc ctt tat aag aat taa tttg gaagagattc 1743 Asp Gln His Asn Gln Asn Cys Leu Tyr Lys Asn * 385 390 acgatttcac catgaggaca cttatctctt tcagtggtcc tcccaagaaa ttatttaaca 1803 aactgaaagg agattttgat taaaattttg cagaggtctt cagtatctat atttgaacac 1863 actgtacaat agtacaaaaa ccaacatagt tggttttcta gtatgaaaga gcaccctcta 1923 gctccatatt ctaagaatct gaaatatgct actatactaa ttaataagta aacttaaggt 1983 gtttaaaaaa ctctgccttc tatattaatt gtaaaatttt gcctctcaga agaatggaat 2043 tggagattgt agacgtggtt ttacaaaatg tgaaatgtct aaatatctgt tcataaaaat 2103 aaaaggaaaa catgtttctt caaaaaaaaa aaa 2136 25 789 DNA Homo sapiens CDS (98)..(664) 25 taacgactca ctatagggaa tttggccctc gaggccaaga attcggcacg agagagcagt 60 taaggcacac agagcaccag ctccctcctg cctgaag atg ttc cac caa att tgg 115 Met Phe His Gln Ile Trp 1 5 gca gct ctg ctc tac ttc tat ggt att atc ctt aac tcc atc tac cag 163 Ala Ala Leu Leu Tyr Phe Tyr Gly Ile Ile Leu Asn Ser Ile Tyr Gln 10 15 20 tgc cct gag cac agt caa ctg aca act ctg ggc gtg gat ggg aag gag 211 Cys Pro Glu His Ser Gln Leu Thr Thr Leu Gly Val Asp Gly Lys Glu 25 30 35 ttc cca gag gtc cac ttg ggc cag tgg tac ttt atc gca ggg gca gct 259 Phe Pro Glu Val His Leu Gly Gln Trp Tyr Phe Ile Ala Gly Ala Ala 40 45 50 ccc acc aag gag gag ttg gca act ttt gac cct gtg gac aac att gtc 307 Pro Thr Lys Glu Glu Leu Ala Thr Phe Asp Pro Val Asp Asn Ile Val 55 60 65 70 ttc aat atg gct gct ggc tct gcc ccg atg cag ctc cac ctt cgt gct 355 Phe Asn Met Ala Ala Gly Ser Ala Pro Met Gln Leu His Leu Arg Ala 75 80 85 acc atc cgc atg aaa gat ggg ctc tgt gtg ccc cgg aaa tgg atc tac 403 Thr Ile Arg Met Lys Asp Gly Leu Cys Val Pro Arg Lys Trp Ile Tyr 90 95 100 cac ctg act gaa ggg agc aca gat ctc aga act gaa ggc cgc cct gac 451 His Leu Thr Glu Gly Ser Thr Asp Leu Arg Thr Glu Gly Arg Pro Asp 105 110 115 atg aag act gag ctc ttt tcc agc tca tgc cca ggt gga atc atg ctg 499 Met Lys Thr Glu Leu Phe Ser Ser Ser Cys Pro Gly Gly Ile Met Leu 120 125 130 aat gag aca ggc cag ggt tac cag cgc ttt ctc ctc tac aat cgc tca 547 Asn Glu Thr Gly Gln Gly Tyr Gln Arg Phe Leu Leu Tyr Asn Arg Ser 135 140 145 150 cca cat cct ccc gaa aag tgt gtg gag gaa ttc aag tcc ctg act tcc 595 Pro His Pro Pro Glu Lys Cys Val Glu Glu Phe Lys Ser Leu Thr Ser 155 160 165 tgc ctg gac tcc aaa gcc ttc tta ttg act cct agg aat caa gag gcc 643 Cys Leu Asp Ser Lys Ala Phe Leu Leu Thr Pro Arg Asn Gln Glu Ala 170 175 180 tgt gag ctg tcc aat aac tga cc tgtaacttca tctaagtccc cagatgggta 696 Cys Glu Leu Ser Asn Asn * 185 caatgggagc tgagttgttg gagggagaag ctggagactt ccagctccag ctcccactca 756 agataataaa gataattttt caaaaaaaaa aaa 789 26 2212 DNA Homo sapiens CDS (452)..(2065) 26 tttaacctgg aatgacttaa atgtcatcct aacttctacc ctctccccaa atgaacggga 60 aagagttttt tctctagccc aatttcacac tgataactgc cagcttcatg agccagacct 120 ccatgaaggc attagagcag ttccccgaga agatcccaat ggaactatca ggcaaattcc 180 ccagcagctg aagactgaca ctgcccgatc gcctcagaag cctcctggac catcgcggat 240 gctttgggta actcttacag tggaggagct ccgtttccct ctgacctggg tcgggcgggc 300 agctgcggct gctgaggctc ggtggggccc ctccaagacg cgtgtccgca tctgcccgcc 360 gggcgtctgc ggggtgcagc gtccactgga gcgcgacagc ccctgggaca gaggaggaca 420 gtggcctcgc ttcccttctc cctcccgcgc g atg gcc tcg gcg ctg agc tat 472 Met Ala Ser Ala Leu Ser Tyr 1 5 gtc tcc aag ttc aag tcc ttc gtg atc ttg ttc gtc acc ccg ctc ctg 520 Val Ser Lys Phe Lys Ser Phe Val Ile Leu Phe Val Thr Pro Leu Leu 10 15 20 ctg ctg cca ctc gtc att ctg atg ccc gcc aag ttt gtc agg tgt gcc 568 Leu Leu Pro Leu Val Ile Leu Met Pro Ala Lys Phe Val Arg Cys Ala 25 30 35 tac gtc atc atc ctc atg gcc att tac tgg tgc aca gaa gtc atc cct 616 Tyr Val Ile Ile Leu Met Ala Ile Tyr Trp Cys Thr Glu Val Ile Pro 40 45 50 55 ctg gct gtc acc tct ctc atg cct gtc ttg ctt ttc cca ctc ttc cag 664 Leu Ala Val Thr Ser Leu Met Pro Val Leu Leu Phe Pro Leu Phe Gln 60 65 70 att ctg gac tcc agg cag gtg tgt gtc cag tac atg aag gac acc aac 712 Ile Leu Asp Ser Arg Gln Val Cys Val Gln Tyr Met Lys Asp Thr Asn 75 80 85 atg ctg ttc ctg ggc ggc ctc atc gtg gcc gtg gct gtg gag cgc tgg 760 Met Leu Phe Leu Gly Gly Leu Ile Val Ala Val Ala Val Glu Arg Trp 90 95 100 aac ctg cac aag agg atc gcc ctg cgc acg ctc ctc tgg gtg ggg gcc 808 Asn Leu His Lys Arg Ile Ala Leu Arg Thr Leu Leu Trp Val Gly Ala 105 110 115 aag cct gca cgg ctg atg ctg ggc ttc atg ggc gtc aca gcc ctc ctg 856 Lys Pro Ala Arg Leu Met Leu Gly Phe Met Gly Val Thr Ala Leu Leu 120 125 130 135 tcc atg tgg atc agt aac acg gca acc acg gcc atg atg gtg ccc atc 904 Ser Met Trp Ile Ser Asn Thr Ala Thr Thr Ala Met Met Val Pro Ile 140 145 150 gtg gag gcc ata ttg cag cag atg gaa gcc aca agc gca gcc acc gag 952 Val Glu Ala Ile Leu Gln Gln Met Glu Ala Thr Ser Ala Ala Thr Glu 155 160 165 gcc ggc ctg gag ctg gtg gac aag ggc aag gcc aag gag ctg cca ggg 1000 Ala Gly Leu Glu Leu Val Asp Lys Gly Lys Ala Lys Glu Leu Pro Gly 170 175 180 agt caa gtg att ttt gaa ggc ccc act ctg ggg cag cag gaa gac caa 1048 Ser Gln Val Ile Phe Glu Gly Pro Thr Leu Gly Gln Gln Glu Asp Gln 185 190 195 gag cgg aag agg ttg tgt aag gcc atg acc ctg tgc atc tgc tac gcg 1096 Glu Arg Lys Arg Leu Cys Lys Ala Met Thr Leu Cys Ile Cys Tyr Ala 200 205 210 215 gcc agc atc ggg ggc acc gcc acc ctg acc ggg acg gga ccc aac gtg 1144 Ala Ser Ile Gly Gly Thr Ala Thr Leu Thr Gly Thr Gly Pro Asn Val 220 225 230 gtg ctc ctg ggc cag atg aac gag ttg ttt cct gac agc aag gac ctc 1192 Val Leu Leu Gly Gln Met Asn Glu Leu Phe Pro Asp Ser Lys Asp Leu 235 240 245 gtg aac ttt gct tcc tgg ttt gca ttt gcc ttt ccc aac atg ctg gtg 1240 Val Asn Phe Ala Ser Trp Phe Ala Phe Ala Phe Pro Asn Met Leu Val 250 255 260 atg ctg ctg ttc gcc tgg ctg tgg ctc cag ttt gtt tac atg aga ttc 1288 Met Leu Leu Phe Ala Trp Leu Trp Leu Gln Phe Val Tyr Met Arg Phe 265 270 275 aat ttt aaa aag tcc tgg ggc tgc ggg cta gag agc aag aaa aac gag 1336 Asn Phe Lys Lys Ser Trp Gly Cys Gly Leu Glu Ser Lys Lys Asn Glu 280 285 290 295 aag gct gcc ctc aag gtg ctg cag gag gag tac cgg aag ctg ggg ccc 1384 Lys Ala Ala Leu Lys Val Leu Gln Glu Glu Tyr Arg Lys Leu Gly Pro 300 305 310 ttg tcc ttc gcg gag atc aac gtg ctg atc tgc ttc ttc ctg ctg gtc 1432 Leu Ser Phe Ala Glu Ile Asn Val Leu Ile Cys Phe Phe Leu Leu Val 315 320 325 atc ctg tgg ttc tcc cga gac ccc ggc ttc atg ccc ggc tgg ctg act 1480 Ile Leu Trp Phe Ser Arg Asp Pro Gly Phe Met Pro Gly Trp Leu Thr 330 335 340 gtt gcc tgg gtg gag ggt gag aca aag tat gtc tcc gat gcc act gtg 1528 Val Ala Trp Val Glu Gly Glu Thr Lys Tyr Val Ser Asp Ala Thr Val 345 350 355 gcc atc ttt gtg gcc acc ctg cta ttc att gtg cct tca cag aag ccc 1576 Ala Ile Phe Val Ala Thr Leu Leu Phe Ile Val Pro Ser Gln Lys Pro 360 365 370 375 aag ttt aac ttc cgc agc cag act gag gaa gaa agg aaa act cca ttt 1624 Lys Phe Asn Phe Arg Ser Gln Thr Glu Glu Glu Arg Lys Thr Pro Phe 380 385 390 tat ccc cct ccc ctg ctg gat tgg aag gta acc cag gag aaa gtg ccc 1672 Tyr Pro Pro Pro Leu Leu Asp Trp Lys Val Thr Gln Glu Lys Val Pro 395 400 405 tgg ggc atc gtg ctg cta cta ggg ggc gga ttt gct ctg gct aaa gga 1720 Trp Gly Ile Val Leu Leu Leu Gly Gly Gly Phe Ala Leu Ala Lys Gly 410 415 420 tcc gag gcc tcg ggg ctg tcc gtg tgg atg ggg aag cag atg gag ccc 1768 Ser Glu Ala Ser Gly Leu Ser Val Trp Met Gly Lys Gln Met Glu Pro 425 430 435 ttg cac gca gtg ccc ccg gca gcc atc acc ttg atc ttg tcc ttg ctc 1816 Leu His Ala Val Pro Pro Ala Ala Ile Thr Leu Ile Leu Ser Leu Leu 440 445 450 455 gtt gcc gtg ttc act gag tgc aca agc aac gtg gcc acc acc acc ttg 1864 Val Ala Val Phe Thr Glu Cys Thr Ser Asn Val Ala Thr Thr Thr Leu 460 465 470 ttc ctg ccc atc ttt gcc tcc atg tct cgc tcc atc ggc ctc aat ccg 1912 Phe Leu Pro Ile Phe Ala Ser Met Ser Arg Ser Ile Gly Leu Asn Pro 475 480 485 ctg tac atc atg ctg ccc tgt acc ctg agt gcc tcc ttt gcc ttc atg 1960 Leu Tyr Ile Met Leu Pro Cys Thr Leu Ser Ala Ser Phe Ala Phe Met 490 495 500 ttg cct gtg gcc acc cct cca aat gcc atc gtg ttc acc tat ggg cac 2008 Leu Pro Val Ala Thr Pro Pro Asn Ala Ile Val Phe Thr Tyr Gly His 505 510 515 ctc aag gtt gct gac atg gta aca cag ctg ttt tta ttt act ccc gtc 2056 Leu Lys Val Ala Asp Met Val Thr Gln Leu Phe Leu Phe Thr Pro Val 520 525 530 535 gga cta taa cgctgtt gtcataaggg atgccccatt tatgaatgac agagtttcaa 2112 Gly Leu * aacgatgtca tgtgacttgg gaatgccacg gaacatccag acctgtagcc attgttgaca 2172 tttataatgc agcttttctt ctttttctga aaaaaaaaaa 2212 27 2024 DNA Homo sapiens CDS (206)..(1909) 27 ttatgaaagc tggtacgcct gcggtaccgg tccggaattc ccgggtcgac gatttcgtgg 60 ggatgtgacg ggcggccctt cgtctcacct tccgtcctcg ggcccgcagg tcgcagggcg 120 gcctgcagct gggccgcggc cgaggaggca gcgcgacctc cgcactattc tttcaacttt 180 taagaacaaa tgcaccttat agctc atg gaa gaa aaa aca caa atc aag aca 232 Met Glu Glu Lys Thr Gln Ile Lys Thr 1 5 ttt ttg ggt tcc aag ttg cca aag tat gga aca aaa tct gta aga agt 280 Phe Leu Gly Ser Lys Leu Pro Lys Tyr Gly Thr Lys Ser Val Arg Ser 10 15 20 25 aca ttg cag cca atg cca aat ggg aca cct gtt aat tta tta gga act 328 Thr Leu Gln Pro Met Pro Asn Gly Thr Pro Val Asn Leu Leu Gly Thr 30 35 40 tcc aag aat agt aat gtc aaa agt tac atc aaa aat aat ggc tct gat 376 Ser Lys Asn Ser Asn Val Lys Ser Tyr Ile Lys Asn Asn Gly Ser Asp 45 50 55 tgt cca tca tct cat tca ttt aat tgg agg aaa gca aat aaa tat cag 424 Cys Pro Ser Ser His Ser Phe Asn Trp Arg Lys Ala Asn Lys Tyr Gln 60 65 70 ctt tgt gca caa ggt gtc gaa gag cct aac aat act caa aat tca cat 472 Leu Cys Ala Gln Gly Val Glu Glu Pro Asn Asn Thr Gln Asn Ser His 75 80 85 gat aaa ata att gat cct gaa aaa cgt gtt cct act caa gga atg ttt 520 Asp Lys Ile Ile Asp Pro Glu Lys Arg Val Pro Thr Gln Gly Met Phe 90 95 100 105 gat aaa aat ggg ata aag gga ggt ttg aaa agt gtt tct tta ttc aca 568 Asp Lys Asn Gly Ile Lys Gly Gly Leu Lys Ser Val Ser Leu Phe Thr 110 115 120 tca aag tta gca aag cca tcc act atg ttt gtg tca tct aca gag gag 616 Ser Lys Leu Ala Lys Pro Ser Thr Met Phe Val Ser Ser Thr Glu Glu 125 130 135 tta aac caa aag tct ttt tct gga cca tct aat ttg ggt aaa ttc acc 664 Leu Asn Gln Lys Ser Phe Ser Gly Pro Ser Asn Leu Gly Lys Phe Thr 140 145 150 aaa ggc aca tta tta gga agg act tca tat tct tcg atc aat act cca 712 Lys Gly Thr Leu Leu Gly Arg Thr Ser Tyr Ser Ser Ile Asn Thr Pro 155 160 165 aaa tca cag ttg aat gga ttt tat gga aac cga tca gct ggt agc atg 760 Lys Ser Gln Leu Asn Gly Phe Tyr Gly Asn Arg Ser Ala Gly Ser Met 170 175 180 185 caa agg cct aga gcg aac tcc tgt gcc acc aga agc agt tct gga gaa 808 Gln Arg Pro Arg Ala Asn Ser Cys Ala Thr Arg Ser Ser Ser Gly Glu 190 195 200 agc tta gct caa tcc cca gac agt agt aaa tct att aat tgt gaa aaa 856 Ser Leu Ala Gln Ser Pro Asp Ser Ser Lys Ser Ile Asn Cys Glu Lys 205 210 215 atg gta agg tca caa agt ttt tca cat tcc att cag aat tca ttc ctt 904 Met Val Arg Ser Gln Ser Phe Ser His Ser Ile Gln Asn Ser Phe Leu 220 225 230 cca cct tca tct ata acc aga tca cat tcc ttt aat aga gct gtg gat 952 Pro Pro Ser Ser Ile Thr Arg Ser His Ser Phe Asn Arg Ala Val Asp 235 240 245 ctt aca aag cct tat cag aac caa cag cta tcc att aga gtg cct cta 1000 Leu Thr Lys Pro Tyr Gln Asn Gln Gln Leu Ser Ile Arg Val Pro Leu 250 255 260 265 cgg tca agt atg cta aca aga aat tcc cgg cag cca gaa gta ctc aat 1048 Arg Ser Ser Met Leu Thr Arg Asn Ser Arg Gln Pro Glu Val Leu Asn 270 275 280 ggg aat gaa cat ttg ggg tat gga ttt aat agg cct tat gct gct ggt 1096 Gly Asn Glu His Leu Gly Tyr Gly Phe Asn Arg Pro Tyr Ala Ala Gly 285 290 295 gga aag aag ttg gct tta cca aat ggc cca ggt gta act tct act tta 1144 Gly Lys Lys Leu Ala Leu Pro Asn Gly Pro Gly Val Thr Ser Thr Leu 300 305 310 ggt tat aga atg gtt cat ccc tct cta ctg aaa tct agc cga tct cca 1192 Gly Tyr Arg Met Val His Pro Ser Leu Leu Lys Ser Ser Arg Ser Pro 315 320 325 ttt tct ggg act atg aca gtt gat gga aat aaa aat tca cct gct gac 1240 Phe Ser Gly Thr Met Thr Val Asp Gly Asn Lys Asn Ser Pro Ala Asp 330 335 340 345 aca tgt gta gag gaa gat gct aca gtt ttg gct aag gac aga gct gct 1288 Thr Cys Val Glu Glu Asp Ala Thr Val Leu Ala Lys Asp Arg Ala Ala 350 355 360 aat aag gac caa gaa ctg att gaa aat gaa agt tat aga aca aaa aac 1336 Asn Lys Asp Gln Glu Leu Ile Glu Asn Glu Ser Tyr Arg Thr Lys Asn 365 370 375 aac cag acc atg aaa cat gat gct aaa atg aga tac ctg agt gat gat 1384 Asn Gln Thr Met Lys His Asp Ala Lys Met Arg Tyr Leu Ser Asp Asp 380 385 390 gtg gat gac att tcc ttg tcg tct ttg tca tct tct gat aag aat gat 1432 Val Asp Asp Ile Ser Leu Ser Ser Leu Ser Ser Ser Asp Lys Asn Asp 395 400 405 tta agt gaa gac ttt agt gat gat ttt ata gat ata gaa gac tcc aac 1480 Leu Ser Glu Asp Phe Ser Asp Asp Phe Ile Asp Ile Glu Asp Ser Asn 410 415 420 425 aga act aga ata act cca gag gaa atg tct ctc aaa gaa gag aaa cat 1528 Arg Thr Arg Ile Thr Pro Glu Glu Met Ser Leu Lys Glu Glu Lys His 430 435 440 gaa aat ggg cca cca cag gat atg ttt gat tcc ccc aag gaa aat gaa 1576 Glu Asn Gly Pro Pro Gln Asp Met Phe Asp Ser Pro Lys Glu Asn Glu 445 450 455 aaa gcc ttc agt aaa act gat gaa tgg ata gat ata agt gtc tct gac 1624 Lys Ala Phe Ser Lys Thr Asp Glu Trp Ile Asp Ile Ser Val Ser Asp 460 465 470 agg agt gaa tgt aca aaa cat act tct ggg aat aat ttg gtt tca cca 1672 Arg Ser Glu Cys Thr Lys His Thr Ser Gly Asn Asn Leu Val Ser Pro 475 480 485 gat aca gac tac aga gct ggt tct tcg ttt gaa ctc tct cca tct gat 1720 Asp Thr Asp Tyr Arg Ala Gly Ser Ser Phe Glu Leu Ser Pro Ser Asp 490 495 500 505 agc tct gat gga aca tac atg tgg gat gaa gaa ggc ttg gaa ccc att 1768 Ser Ser Asp Gly Thr Tyr Met Trp Asp Glu Glu Gly Leu Glu Pro Ile 510 515 520 gga aat gtc cat cca gtt ggg agc tat gag tcc tct gaa atg aac agc 1816 Gly Asn Val His Pro Val Gly Ser Tyr Glu Ser Ser Glu Met Asn Ser 525 530 535 ata gta tgt atg gat tta tat act ctt gga ata ttt tgt tta ccc tac 1864 Ile Val Cys Met Asp Leu Tyr Thr Leu Gly Ile Phe Cys Leu Pro Tyr 540 545 550 tat aga gag act tgt gat atg att gat ttt gta aaa aat tta tga att 1912 Tyr Arg Glu Thr Cys Asp Met Ile Asp Phe Val Lys Asn Leu * 555 560 565 aactttacta ctttgagaaa tggaaattca tatttgttaa gagcctataa aatatctgac 1972 tctaatatga aataaagcat ggagaatata tgacatttga aaaaaaaaaa aa 2024 28 816 DNA Homo sapiens CDS (109)..(588) 28 atcgacagct tctgacgcct gtggtaccgg tccggaattc ccgggtcgac ccacgcgtcc 60 gcccacgcgt ccgcacgtaa cggagtggcc aacggcctgc agagcaac atg ccc aag 117 Met Pro Lys 1 ttt tat tgt gac tac tgc gat aca tac ctc acc cat gac tct cca tct 165 Phe Tyr Cys Asp Tyr Cys Asp Thr Tyr Leu Thr His Asp Ser Pro Ser 5 10 15 gtg aga aag aca cac tgc agt gga agg aaa cac aaa gag aat gtg aaa 213 Val Arg Lys Thr His Cys Ser Gly Arg Lys His Lys Glu Asn Val Lys 20 25 30 35 gac tat tat cag aaa tgg atg gaa gag cag gct cag agc ctg att gac 261 Asp Tyr Tyr Gln Lys Trp Met Glu Glu Gln Ala Gln Ser Leu Ile Asp 40 45 50 aaa aca acg gct gca ttt caa caa gga aag ata cct cct act cca ttc 309 Lys Thr Thr Ala Ala Phe Gln Gln Gly Lys Ile Pro Pro Thr Pro Phe 55 60 65 tct gct cct cct cct gca ggg gcg atg ata cca cct ccc ccc agc ctt 357 Ser Ala Pro Pro Pro Ala Gly Ala Met Ile Pro Pro Pro Pro Ser Leu 70 75 80 ccg ggt cct cct cgc cct ggt atg atg cca gca ccc cat atg ggg ggc 405 Pro Gly Pro Pro Arg Pro Gly Met Met Pro Ala Pro His Met Gly Gly 85 90 95 cct ccc atg atg cca atg atg ggc cct cct cct cct ggg atg atg cca 453 Pro Pro Met Met Pro Met Met Gly Pro Pro Pro Pro Gly Met Met Pro 100 105 110 115 gtg gga cct gct cct gga atg agg ccg ccc atg gga ggc cat atg cca 501 Val Gly Pro Ala Pro Gly Met Arg Pro Pro Met Gly Gly His Met Pro 120 125 130 atg atg cct ggg ccc cca atg atg aga cct cct gcc cgt ccc atg atg 549 Met Met Pro Gly Pro Pro Met Met Arg Pro Pro Ala Arg Pro Met Met 135 140 145 gtg ccc act cgg ccc gga atg act cga cca gac aga taa ggatagaggg 598 Val Pro Thr Arg Pro Gly Met Thr Arg Pro Asp Arg * 150 155 160 gaggccttat tgtatcggtt ttatattacc tgttctgctt caccaggaga tcatgctgct 658 gtgatactga gttttctaaa cagcataagg aagacttgct cccctgtcct atgaaagaga 718 atagttttgg aggggagaag tgggacaaaa aagatgcagt tttcctttgt attgggaaat 778 gtgaaaataa aattgtcaac tctttcaaaa aaaaaaaa 816 29 3075 DNA Homo sapiens CDS (69)..(2789) 29 ggtgggttta tctcaaggcc tgagtagccg gtaacaaacg agggttcccg ggattggacc 60 gacgcacc atg cct ctg cga ctt gat atc aaa aga aag cta act gct aga 110 Met Pro Leu Arg Leu Asp Ile Lys Arg Lys Leu Thr Ala Arg 1 5 10 tct gat cga gtt aag agt gtg gat ctg cat cct aca gag cca tgg atg 158 Ser Asp Arg Val Lys Ser Val Asp Leu His Pro Thr Glu Pro Trp Met 15 20 25 30 ttg gca agt ctt tac aat ggc agt gtg tgt gtt tgg aat cat gaa aca 206 Leu Ala Ser Leu Tyr Asn Gly Ser Val Cys Val Trp Asn His Glu Thr 35 40 45 cag aca ctg gtg aag aca ttt gaa gta tgt gat ctt cct gtt cga gct 254 Gln Thr Leu Val Lys Thr Phe Glu Val Cys Asp Leu Pro Val Arg Ala 50 55 60 gca aag ttt gtt gca agg aag aat tgg gtt gtg aca gga gcg gat gac 302 Ala Lys Phe Val Ala Arg Lys Asn Trp Val Val Thr Gly Ala Asp Asp 65 70 75 atg cag att aga gtg ttc aat tac aat act ctg gag aga gtt cat atg 350 Met Gln Ile Arg Val Phe Asn Tyr Asn Thr Leu Glu Arg Val His Met 80 85 90 ttt gaa gca cac tca gac tac att cgc tgt att gct gtt cat cca acc 398 Phe Glu Ala His Ser Asp Tyr Ile Arg Cys Ile Ala Val His Pro Thr 95 100 105 110 cag cct ttc att cta act agc agt gat gac atg ctt att aag ctc tgg 446 Gln Pro Phe Ile Leu Thr Ser Ser Asp Asp Met Leu Ile Lys Leu Trp 115 120 125 gac tgg gat aaa aaa tgg tct tgc tca caa gtg ttt gaa gga cac acc 494 Asp Trp Asp Lys Lys Trp Ser Cys Ser Gln Val Phe Glu Gly His Thr 130 135 140 cat tat gtt atg cag att gtg atc aac ccc aaa gat aac aat cag ttt 542 His Tyr Val Met Gln Ile Val Ile Asn Pro Lys Asp Asn Asn Gln Phe 145 150 155 gcc agt gcc tct ttg gac agg act atc aag gtg tgg cag ttg ggc tct 590 Ala Ser Ala Ser Leu Asp Arg Thr Ile Lys Val Trp Gln Leu Gly Ser 160 165 170 tcg tca cca aac ttc act ttg gaa gga cat gag aaa ggc gtg aat tgc 638 Ser Ser Pro Asn Phe Thr Leu Glu Gly His Glu Lys Gly Val Asn Cys 175 180 185 190 att gat tac tac agt ggt ggg gac aag cca tac ctc att tca ggt gca 686 Ile Asp Tyr Tyr Ser Gly Gly Asp Lys Pro Tyr Leu Ile Ser Gly Ala 195 200 205 gat gac cgt ctt gtt aaa ata tgg gat tat cag aat aaa aca tgt gtg 734 Asp Asp Arg Leu Val Lys Ile Trp Asp Tyr Gln Asn Lys Thr Cys Val 210 215 220 cag aca ctg gaa gga cat gcc caa aat gtg tct tgt gcc agc ttt cat 782 Gln Thr Leu Glu Gly His Ala Gln Asn Val Ser Cys Ala Ser Phe His 225 230 235 cct gag ttg cca atc att atc aca ggt tca gaa gat gga aca gta cgt 830 Pro Glu Leu Pro Ile Ile Ile Thr Gly Ser Glu Asp Gly Thr Val Arg 240 245 250 att tgg cat tca agc acc tac cgg ctt gag agc aca ctg aat tat gga 878 Ile Trp His Ser Ser Thr Tyr Arg Leu Glu Ser Thr Leu Asn Tyr Gly 255 260 265 270 atg gag agg gta tgg tgc gtg gcc agt cta aga ggg tca aac aat gtc 926 Met Glu Arg Val Trp Cys Val Ala Ser Leu Arg Gly Ser Asn Asn Val 275 280 285 gct ttg ggc tat gat gaa ggg agc atc att gtt aag ctt ggt cgg gag 974 Ala Leu Gly Tyr Asp Glu Gly Ser Ile Ile Val Lys Leu Gly Arg Glu 290 295 300 gaa cct gcc atg tcc atg gat gcc aat gga aag ata att tgg gcc aag 1022 Glu Pro Ala Met Ser Met Asp Ala Asn Gly Lys Ile Ile Trp Ala Lys 305 310 315 cat tca gaa gtc cag cag gcc aac cta aaa gca atg gga gat gct gaa 1070 His Ser Glu Val Gln Gln Ala Asn Leu Lys Ala Met Gly Asp Ala Glu 320 325 330 att aaa gat ggt gaa aga ttg cca ctg gca gta aag gat atg ggc agt 1118 Ile Lys Asp Gly Glu Arg Leu Pro Leu Ala Val Lys Asp Met Gly Ser 335 340 345 350 tgt gaa ata tac cct cag act att cag cac aat cct aat ggg cgg ttt 1166 Cys Glu Ile Tyr Pro Gln Thr Ile Gln His Asn Pro Asn Gly Arg Phe 355 360 365 gtg gtg gtg tgt ggt gat ggg gag tat atc atc tac aca gca atg gca 1214 Val Val Val Cys Gly Asp Gly Glu Tyr Ile Ile Tyr Thr Ala Met Ala 370 375 380 ttg aga aac aag agc ttt gga tct gct cag gag ttt gca tgg gcc cac 1262 Leu Arg Asn Lys Ser Phe Gly Ser Ala Gln Glu Phe Ala Trp Ala His 385 390 395 gat tct tca gag tat gca ata aga gag agc aac agc att gta aag ata 1310 Asp Ser Ser Glu Tyr Ala Ile Arg Glu Ser Asn Ser Ile Val Lys Ile 400 405 410 ttt aag aac ttt aag gaa aaa aaa tca ttt aaa cca gat ttt gga gca 1358 Phe Lys Asn Phe Lys Glu Lys Lys Ser Phe Lys Pro Asp Phe Gly Ala 415 420 425 430 gaa agt atc tac ggc ggc ttc tta ttg gga gtc aga tct gta aat ggc 1406 Glu Ser Ile Tyr Gly Gly Phe Leu Leu Gly Val Arg Ser Val Asn Gly 435 440 445 tta gcc ttc tat gac tgg gac aat aca gaa ctc ata cga aga att gaa 1454 Leu Ala Phe Tyr Asp Trp Asp Asn Thr Glu Leu Ile Arg Arg Ile Glu 450 455 460 att cag ccc aaa cat att ttc tgg tct gac tct gga gag cta gtc tgt 1502 Ile Gln Pro Lys His Ile Phe Trp Ser Asp Ser Gly Glu Leu Val Cys 465 470 475 att gct act gag gaa tca ttt ttt atc ctt aag tat ctg tca gaa aaa 1550 Ile Ala Thr Glu Glu Ser Phe Phe Ile Leu Lys Tyr Leu Ser Glu Lys 480 485 490 gtc ttg gct gca cag gaa aca cat gag gga gtt act gaa gat ggc att 1598 Val Leu Ala Ala Gln Glu Thr His Glu Gly Val Thr Glu Asp Gly Ile 495 500 505 510 gaa gat gcc ttt gag gtt ctt ggt gag att cag gaa att gtg aaa aca 1646 Glu Asp Ala Phe Glu Val Leu Gly Glu Ile Gln Glu Ile Val Lys Thr 515 520 525 ggg ctt tgg gta ggc gat tgc ttc att tac aca agt tct gtg aac aga 1694 Gly Leu Trp Val Gly Asp Cys Phe Ile Tyr Thr Ser Ser Val Asn Arg 530 535 540 tta aat tat tat gtt gga gga gaa ata gtc acc att gcc cac ttg gac 1742 Leu Asn Tyr Tyr Val Gly Gly Glu Ile Val Thr Ile Ala His Leu Asp 545 550 555 agg acg atg tat ctc cta ggc tac att cct aaa gac aac agg ctt tat 1790 Arg Thr Met Tyr Leu Leu Gly Tyr Ile Pro Lys Asp Asn Arg Leu Tyr 560 565 570 ctg ggg gat aaa gaa ttg aac atc att agc tat tcc ctg ctg gtt tca 1838 Leu Gly Asp Lys Glu Leu Asn Ile Ile Ser Tyr Ser Leu Leu Val Ser 575 580 585 590 gtc ctg gaa tac cag aca gct gtc atg cgg agg gac ttt agc atg gct 1886 Val Leu Glu Tyr Gln Thr Ala Val Met Arg Arg Asp Phe Ser Met Ala 595 600 605 gat aag gtc ctt cct acc att cca aaa gaa cag agg acc aga gtt gca 1934 Asp Lys Val Leu Pro Thr Ile Pro Lys Glu Gln Arg Thr Arg Val Ala 610 615 620 cac ttt ttg gaa aag cag ggc ttc aag cag caa gct ctt aca gta tcc 1982 His Phe Leu Glu Lys Gln Gly Phe Lys Gln Gln Ala Leu Thr Val Ser 625 630 635 aca gat cct gag cat cgt ttt gag ctt gct ctt cag ctt gga gag tta 2030 Thr Asp Pro Glu His Arg Phe Glu Leu Ala Leu Gln Leu Gly Glu Leu 640 645 650 aaa att gca tac cag tta gca gtg gaa gca gag tca gaa cag aag tgg 2078 Lys Ile Ala Tyr Gln Leu Ala Val Glu Ala Glu Ser Glu Gln Lys Trp 655 660 665 670 aaa caa ctt gct gaa ctt gcc att agt aaa tgt cag ttt ggc cta gcc 2126 Lys Gln Leu Ala Glu Leu Ala Ile Ser Lys Cys Gln Phe Gly Leu Ala 675 680 685 cag gag tgc ctg cat cat gca cag gat tat ggg ggc ctg ctg ctt ttg 2174 Gln Glu Cys Leu His His Ala Gln Asp Tyr Gly Gly Leu Leu Leu Leu 690 695 700 gcc act gcc tct gga aat gct aat atg gtg aac aag cta gca gag ggt 2222 Ala Thr Ala Ser Gly Asn Ala Asn Met Val Asn Lys Leu Ala Glu Gly 705 710 715 gcg gag aga gat ggc aaa aat aat gtg gca ttc atg agc tac ttt tta 2270 Ala Glu Arg Asp Gly Lys Asn Asn Val Ala Phe Met Ser Tyr Phe Leu 720 725 730 cag ggc aag gtt gat gcc tgc cta gag ctc tta att aga act gga cgg 2318 Gln Gly Lys Val Asp Ala Cys Leu Glu Leu Leu Ile Arg Thr Gly Arg 735 740 745 750 ctg cca gaa gct gcc ttc ttg gcc cga act tac tta ccc agt cag gtt 2366 Leu Pro Glu Ala Ala Phe Leu Ala Arg Thr Tyr Leu Pro Ser Gln Val 755 760 765 tca agg gta gtg aaa ctc tgg aga gag aat ctc tca aaa gtc aat cag 2414 Ser Arg Val Val Lys Leu Trp Arg Glu Asn Leu Ser Lys Val Asn Gln 770 775 780 aaa gca gca gaa tcc ctt gct gac cca aca gag tat gaa aac ctg ttc 2462 Lys Ala Ala Glu Ser Leu Ala Asp Pro Thr Glu Tyr Glu Asn Leu Phe 785 790 795 cct gga tta aaa gaa gcc ttt gtt gtt gaa gaa tgg gtg aag gaa aca 2510 Pro Gly Leu Lys Glu Ala Phe Val Val Glu Glu Trp Val Lys Glu Thr 800 805 810 cat gct gat ctg tgg cca gcc aaa caa tac cca ctt gtc acg cca aat 2558 His Ala Asp Leu Trp Pro Ala Lys Gln Tyr Pro Leu Val Thr Pro Asn 815 820 825 830 gaa gag aga aat gtc atg gaa gag gga aaa gac ttt cag ccc tca aga 2606 Glu Glu Arg Asn Val Met Glu Glu Gly Lys Asp Phe Gln Pro Ser Arg 835 840 845 tct aca gct caa cag gaa ctt gat ggg aaa cct gct tct cct act ccg 2654 Ser Thr Ala Gln Gln Glu Leu Asp Gly Lys Pro Ala Ser Pro Thr Pro 850 855 860 gtt att gtg gcc tcc cac aca gcc aac aaa gaa gaa aag agt tta ctc 2702 Val Ile Val Ala Ser His Thr Ala Asn Lys Glu Glu Lys Ser Leu Leu 865 870 875 gaa cta gaa gta gat ttg gat aat ttg gaa tta gaa gat att gac aca 2750 Glu Leu Glu Val Asp Leu Asp Asn Leu Glu Leu Glu Asp Ile Asp Thr 880 885 890 aca gat atc aat ctg gat gaa gat att ttg gat gat tga ctgtaatgct 2799 Thr Asp Ile Asn Leu Asp Glu Asp Ile Leu Asp Asp * 895 900 905 ttccatttac ctgactaaac agatcattat tatatatagg tattgattgc taccctgacc 2859 acagtgcttt ggactatgag aaacttctta gatttttata tgtaaatgct gtggaccact 2919 gggagcacaa tgcccacatc atcttaagaa gagtttatgt gcagcattta aatcactgtg 2979 ttttccttgt taactaaaac agacatgggc tttgattttt ttcatactat tagaccatat 3039 ctcataaaac cttttgaatt aataaaaaaa aaaaaa 3075 30 3069 DNA Homo sapiens CDS (1)..(2652) 30 atg aat aca tca caa tta tta gaa ata gcc aac cag gtg ttt gta aac 48 Met Asn Thr Ser Gln Leu Leu Glu Ile Ala Asn Gln Val Phe Val Asn 1 5 10 15 agg gct gca gta agc ctt gag gaa aac cgc aaa gag aat gga cat cag 96 Arg Ala Ala Val Ser Leu Glu Glu Asn Arg Lys Glu Asn Gly His Gln 20 25 30 gcc cgg cga aac acc gac ctg gtt gtc agc tgc agc aat cag agg ggt 144 Ala Arg Arg Asn Thr Asp Leu Val Val Ser Cys Ser Asn Gln Arg Gly 35 40 45 cag gag tca ctg gaa aag ttg tta ggc cgg tat ttc tac atc tcg cat 192 Gln Glu Ser Leu Glu Lys Leu Leu Gly Arg Tyr Phe Tyr Ile Ser His 50 55 60 ttg tca gcc ctc gcc aaa acc atg agg cag cgg ttt gtt acc tgc cga 240 Leu Ser Ala Leu Ala Lys Thr Met Arg Gln Arg Phe Val Thr Cys Arg 65 70 75 80 cac cat aat gcg agg caa ggt cca gct gtt ccg ccc ggc ata caa gct 288 His His Asn Ala Arg Gln Gly Pro Ala Val Pro Pro Gly Ile Gln Ala 85 90 95 tat gca gca gcc ccc att gaa gat ctg cag gcc att agg aac aat atc 336 Tyr Ala Ala Ala Pro Ile Glu Asp Leu Gln Ala Ile Arg Asn Asn Ile 100 105 110 aca gcg ggt gtt tac aca ccc tgc gat att gga ggt aat atc atc ctc 384 Thr Ala Gly Val Tyr Thr Pro Cys Asp Ile Gly Gly Asn Ile Ile Leu 115 120 125 tgc ccc ctg gca tat tac caa cga tat caa aca ggg gtg gtg tac acc 432 Cys Pro Leu Ala Tyr Tyr Gln Arg Tyr Gln Thr Gly Val Val Tyr Thr 130 135 140 cct tgt gat att ggg agt att atc atc ctc tcc acc tcc ggg tgt cca 480 Pro Cys Asp Ile Gly Ser Ile Ile Ile Leu Ser Thr Ser Gly Cys Pro 145 150 155 160 agt cac aca gag cca cgg aat ctc aca ggt gtc tca gaa ttc ctc ctc 528 Ser His Thr Glu Pro Arg Asn Leu Thr Gly Val Ser Glu Phe Leu Leu 165 170 175 ctg gga ctc tca gag gat cca gaa ctg cag cct gtc ctc cct ggg ctg 576 Leu Gly Leu Ser Glu Asp Pro Glu Leu Gln Pro Val Leu Pro Gly Leu 180 185 190 tcc ctg tcc atg tat ctg ctc acg gtg ctg agg aac ctg ctc atc atc 624 Ser Leu Ser Met Tyr Leu Leu Thr Val Leu Arg Asn Leu Leu Ile Ile 195 200 205 ctg gct gtc agc tct gac tcc cac ctc cac acc ccc atg tac ttc ttc 672 Leu Ala Val Ser Ser Asp Ser His Leu His Thr Pro Met Tyr Phe Phe 210 215 220 ctc tcc aac ccg tca tgg gct gac atc gct ttc acc tcg gcc aca gtt 720 Leu Ser Asn Pro Ser Trp Ala Asp Ile Ala Phe Thr Ser Ala Thr Val 225 230 235 240 ccc aag atg att gtg gac atg cag agt ggt gtg gtg gtg tca gtg atg 768 Pro Lys Met Ile Val Asp Met Gln Ser Gly Val Val Val Ser Val Met 245 250 255 tac act gtg gtc acc ccc atg ctg aac cct ttc atc tac tgc ctg aga 816 Tyr Thr Val Val Thr Pro Met Leu Asn Pro Phe Ile Tyr Cys Leu Arg 260 265 270 aac agg gac att caa agc gcc ctg tgg agg ctg cgc agc aga aca gtc 864 Asn Arg Asp Ile Gln Ser Ala Leu Trp Arg Leu Arg Ser Arg Thr Val 275 280 285 gaa tct cat gat ctg ttc cat cct ttt tct tgt gtg ggt atc cac tgt 912 Glu Ser His Asp Leu Phe His Pro Phe Ser Cys Val Gly Ile His Cys 290 295 300 cag gtc tct gag ctt gat gct gtc atg tcc ctt gac acc gct tcc ggg 960 Gln Val Ser Glu Leu Asp Ala Val Met Ser Leu Asp Thr Ala Ser Gly 305 310 315 320 gct ttt cgg tgg atg gct ttt ggg gtg gaa gtg gca gcc cca gct tac 1008 Ala Phe Arg Trp Met Ala Phe Gly Val Glu Val Ala Ala Pro Ala Tyr 325 330 335 cag cca tca tgc tca tgt ccg gga tct cag tcc tct ggg gaa ggg gcc 1056 Gln Pro Ser Cys Ser Cys Pro Gly Ser Gln Ser Ser Gly Glu Gly Ala 340 345 350 aga aaa ggc tgg agc agc cga agt ctt tcg gaa aca gta tct gcg gta 1104 Arg Lys Gly Trp Ser Ser Arg Ser Leu Ser Glu Thr Val Ser Ala Val 355 360 365 tat tca ggg ctg act cag gaa aga aga tgc cag ccc cag agt ccc acc 1152 Tyr Ser Gly Leu Thr Gln Glu Arg Arg Cys Gln Pro Gln Ser Pro Thr 370 375 380 tcc acc gtt ggt tcc atc ata atg aat gga tcc aat atg gca aat aca 1200 Ser Thr Val Gly Ser Ile Ile Met Asn Gly Ser Asn Met Ala Asn Thr 385 390 395 400 tca ccg agt gta aaa tcc aaa gag gac cag ggg tta agt ggg cac gat 1248 Ser Pro Ser Val Lys Ser Lys Glu Asp Gln Gly Leu Ser Gly His Asp 405 410 415 gaa aag gaa aac cca ttt gca gag tac atg tgg atg gag aat gaa gag 1296 Glu Lys Glu Asn Pro Phe Ala Glu Tyr Met Trp Met Glu Asn Glu Glu 420 425 430 gat ttc aac aga cag gtg gag gag gaa ctg cag gag caa gac ttc ttg 1344 Asp Phe Asn Arg Gln Val Glu Glu Glu Leu Gln Glu Gln Asp Phe Leu 435 440 445 gac cgc tgc ttc caa gag atg ctg gat gaa gaa gac caa gac tgg ttt 1392 Asp Arg Cys Phe Gln Glu Met Leu Asp Glu Glu Asp Gln Asp Trp Phe 450 455 460 att ccc tca cga gac ctg cct cag gcc atg gga cag ttg caa cag cag 1440 Ile Pro Ser Arg Asp Leu Pro Gln Ala Met Gly Gln Leu Gln Gln Gln 465 470 475 480 tta aat gga ctg tca gtc agt gaa ggt cat gat tct gaa gat att ttg 1488 Leu Asn Gly Leu Ser Val Ser Glu Gly His Asp Ser Glu Asp Ile Leu 485 490 495 gtc cat ggg cgc agg tcc ctg agc cca cag ctt cgc ggg ggt ctg gcc 1536 Val His Gly Arg Arg Ser Leu Ser Pro Gln Leu Arg Gly Gly Leu Ala 500 505 510 gag cat gcg tca caa cct acg cgg cca aga gca gtg cgc acg cgc aac 1584 Glu His Ala Ser Gln Pro Thr Arg Pro Arg Ala Val Arg Thr Arg Asn 515 520 525 cta acg cgg gac tgc cag caa ctt ccg ggc gtt tac agg cag gca gga 1632 Leu Thr Arg Asp Cys Gln Gln Leu Pro Gly Val Tyr Arg Gln Ala Gly 530 535 540 tcc agg agg acg gga ggg gcc gct gcg gac cgc agt cgc tcc acc tgg 1680 Ser Arg Arg Thr Gly Gly Ala Ala Ala Asp Arg Ser Arg Ser Thr Trp 545 550 555 560 agg aga cac cag aag gaa gac agc ctg agg gac gca gcc atc ccc ggc 1728 Arg Arg His Gln Lys Glu Asp Ser Leu Arg Asp Ala Ala Ile Pro Gly 565 570 575 tcc tac cgg cgc ccc gcc ccg cgc atg cgc acg cgc aca ggg agt cag 1776 Ser Tyr Arg Arg Pro Ala Pro Arg Met Arg Thr Arg Thr Gly Ser Gln 580 585 590 ctg gct gcg cgg gag gtc acg gga agt ggg gcg gtg ccc aga cag ctg 1824 Leu Ala Ala Arg Glu Val Thr Gly Ser Gly Ala Val Pro Arg Gln Leu 595 600 605 gag gga agg agg tgt cag gcg ggg aga gac gca aac ggc ggg acc agc 1872 Glu Gly Arg Arg Cys Gln Ala Gly Arg Asp Ala Asn Gly Gly Thr Ser 610 615 620 agc gac ggt agc agc agc atg gcc gcg atc tat ggg ggt gta gag ggg 1920 Ser Asp Gly Ser Ser Ser Met Ala Ala Ile Tyr Gly Gly Val Glu Gly 625 630 635 640 gga ggc aca cga tcc gag gtc ctt tta gtc tca gag gat ggg aag atc 1968 Gly Gly Thr Arg Ser Glu Val Leu Leu Val Ser Glu Asp Gly Lys Ile 645 650 655 ctg gca gaa gca gat gga ctg agc aca aac cac tgg ctg atc ggg aca 2016 Leu Ala Glu Ala Asp Gly Leu Ser Thr Asn His Trp Leu Ile Gly Thr 660 665 670 gac aag tgt gtg gag agg atc aat gag atg gtg aac agg gcc aaa cgg 2064 Asp Lys Cys Val Glu Arg Ile Asn Glu Met Val Asn Arg Ala Lys Arg 675 680 685 aaa gca ggg gtg gat cct ctg gta ccg ctg cga agc ttg ggc cta tct 2112 Lys Ala Gly Val Asp Pro Leu Val Pro Leu Arg Ser Leu Gly Leu Ser 690 695 700 ctg agc ggt ggg gac cag gag gac gcg ggg agg atc ctg atc gag gag 2160 Leu Ser Gly Gly Asp Gln Glu Asp Ala Gly Arg Ile Leu Ile Glu Glu 705 710 715 720 ctg agg gac cga ttt ccc tac ctg agt gaa agc tac tta atc acc acc 2208 Leu Arg Asp Arg Phe Pro Tyr Leu Ser Glu Ser Tyr Leu Ile Thr Thr 725 730 735 gat gcc gcc ggc tcc atc gcc aca gct aca ccg gat ggt gga gtt gtg 2256 Asp Ala Ala Gly Ser Ile Ala Thr Ala Thr Pro Asp Gly Gly Val Val 740 745 750 ctc ata tct gga aca ggc tcc aac tgc agg ctc atc aac cct gat ggc 2304 Leu Ile Ser Gly Thr Gly Ser Asn Cys Arg Leu Ile Asn Pro Asp Gly 755 760 765 tcc gag agt ggc tgc ggc ggc tgg ggc cat atg atg ggt gat gag ggt 2352 Ser Glu Ser Gly Cys Gly Gly Trp Gly His Met Met Gly Asp Glu Gly 770 775 780 tca gcc tac tgg atc gca cac caa gca gtg aaa ata gtg ttt gac tcc 2400 Ser Ala Tyr Trp Ile Ala His Gln Ala Val Lys Ile Val Phe Asp Ser 785 790 795 800 att gac aac cta gag gcg gct cct cat gat atc ggc tac gtc aaa cag 2448 Ile Asp Asn Leu Glu Ala Ala Pro His Asp Ile Gly Tyr Val Lys Gln 805 810 815 gcc atg ttc cac tat ttc cag gtg cca gat cgg cta ggg ata ctc act 2496 Ala Met Phe His Tyr Phe Gln Val Pro Asp Arg Leu Gly Ile Leu Thr 820 825 830 cac ctg tat agg gac ttt gat aaa tgc agg ttt gct ggg ttt tgc cgg 2544 His Leu Tyr Arg Asp Phe Asp Lys Cys Arg Phe Ala Gly Phe Cys Arg 835 840 845 aaa att gca gaa ggt gct cag cag gga gac ccc ctt tcc cgc tat atc 2592 Lys Ile Ala Glu Gly Ala Gln Gln Gly Asp Pro Leu Ser Arg Tyr Ile 850 855 860 ttc agg aag agc tgg gga gat gct ggg cag gca cat cgt agc agt gtt 2640 Phe Arg Lys Ser Trp Gly Asp Ala Gly Gln Ala His Arg Ser Ser Val 865 870 875 880 gcc cga gat tga ccc ggtcttgttc cagggcaaga ttggactccc catcctgtgc 2695 Ala Arg Asp * gtgggctctg tgtggaagag ctgggagctg ctgaaggaag gttttctttt ggcgctgacc 2755 cagggcagag agatccaagc tcagaacttc ttctccagct tcaccctgat gaagctgagg 2815 cactcctccg ctctgggtgg ggccagccta ggggccaggc acatcgggca cctcctcccc 2875 atggactata gcgccaatgc cattgccttc tattcctaca ccttttccta gggggctggt 2935 cccggctcca ccccctccaa gctcagtgga cactgggtct gaaaggaagg agtcttttgc 2995 ttcctttctc ctttttacaa aaacaaacat agaagaaaat aaatgcactt tatccactcc 3055 ccaaaaaaaa aaaa 3069 31 777 DNA Homo sapiens CDS (373)..(570) 31 atttggccct cgaggccaag aattcggcac gagacacgga gggtgggagc agtggatggt 60 gggagggaat ggagataata aatggaacaa caactatctt attaaaataa gataataaca 120 gtcaaaacta atacaaagca tataaaacca ggtaagatga taaacatgaa tgccgaaaac 180 tgcttaagaa aagggtagca gggagttatt ttctgagtag atgacattta tgctaaacgt 240 ggaacaagga gatggagcca accctgaaaa ttctgggaga agaggacaga aggcagaggg 300 aagagcaaga gcaaaaattc tgaaacagga gaaattgtga gcatatcagc attaagtacc 360 actgaggtgg ca atg cac act tca acc tct tct tca gtc aca aag agt 408 Met His Thr Ser Thr Ser Ser Ser Val Thr Lys Ser 1 5 10 tac atc tca tca cag aca aat gga gaa acg gga caa ctt gtc cat cgt 456 Tyr Ile Ser Ser Gln Thr Asn Gly Glu Thr Gly Gln Leu Val His Arg 15 20 25 ttc act gta cca gct cct gta gtg ata ata ctc att att ttg tgt gtg 504 Phe Thr Val Pro Ala Pro Val Val Ile Ile Leu Ile Ile Leu Cys Val 30 35 40 atg gct ggt att att gga acg atc ctc tta att tct tac agt att cgc 552 Met Ala Gly Ile Ile Gly Thr Ile Leu Leu Ile Ser Tyr Ser Ile Arg 45 50 55 60 cga ctg ata aag gca tga ggatgt ggcctgcatg ctgcctgatc ttgcctagaa 606 Arg Leu Ile Lys Ala * 65 ccggctgcac ctgctgttct cttgtttatg caaactggct gcacctgcta ttcctttgct 666 tatgccccta cccctggcta tcctaattcc ctgttctcct gcctcactat tactgtattc 726 tctacttcta aataaaaata aaacaaaata caaaccgtta aaaaaaaaaa a 777 32 1474 DNA Homo sapiens CDS (274)..(933) 32 aaggatcctt aattaaatta atccccctcc cccggagctt tctcgcgggc ttgcagctgc 60 ggcaagtgct ggcggcggct gctcgcgcaa gtcagctggc gtgggaacta ccctttgtag 120 ctgagaacgg cttgtttatt gctacaaaga ctctattgac attggtagct tcagcggcag 180 cagcttctta cggtataaag ctgttgcttc ctgaagaggc tacaagcatc cttccctagg 240 actgctgtaa gctttgagcc tctagcagga gac atg cct cgg gga cga aag agt 294 Met Pro Arg Gly Arg Lys Ser 1 5 cgg cgc cgc cgt aat gcg aga gcc gca gaa gag aac cgc aac aat cgc 342 Arg Arg Arg Arg Asn Ala Arg Ala Ala Glu Glu Asn Arg Asn Asn Arg 10 15 20 aaa atc cag gcc tca gag gcc tcc gag acc cct atg gcc gcc tct gtg 390 Lys Ile Gln Ala Ser Glu Ala Ser Glu Thr Pro Met Ala Ala Ser Val 25 30 35 gta gcg agc acc ccc gaa gac gac ctg agc ggc ccc gag gaa gac ccg 438 Val Ala Ser Thr Pro Glu Asp Asp Leu Ser Gly Pro Glu Glu Asp Pro 40 45 50 55 agc act cca gag gag gcc tct acc acc cct gaa gaa gcc tcg agc act 486 Ser Thr Pro Glu Glu Ala Ser Thr Thr Pro Glu Glu Ala Ser Ser Thr 60 65 70 gcc caa gca caa aag cct tca gtg ccc cgg agc aat ttt cag ggc acc 534 Ala Gln Ala Gln Lys Pro Ser Val Pro Arg Ser Asn Phe Gln Gly Thr 75 80 85 aag aaa agt ctc ctg atg tct ata tta gcg ctc atc ttc atc atg ggc 582 Lys Lys Ser Leu Leu Met Ser Ile Leu Ala Leu Ile Phe Ile Met Gly 90 95 100 aac agc gcc aag gaa gct ctg gtc tgg aaa gtg ctg ggg aag tta gga 630 Asn Ser Ala Lys Glu Ala Leu Val Trp Lys Val Leu Gly Lys Leu Gly 105 110 115 atg cag cct gga cgt cag cac agc atc ttt gga gat ccg aag aag atc 678 Met Gln Pro Gly Arg Gln His Ser Ile Phe Gly Asp Pro Lys Lys Ile 120 125 130 135 gtc aca gaa gag ttt gtg cgc aga ggg tac ctg att tat aaa ccg gtg 726 Val Thr Glu Glu Phe Val Arg Arg Gly Tyr Leu Ile Tyr Lys Pro Val 140 145 150 ccc cgt agc agt ccg gtg gag tat gag ttc ttc tgg ggg ccc cga gca 774 Pro Arg Ser Ser Pro Val Glu Tyr Glu Phe Phe Trp Gly Pro Arg Ala 155 160 165 cac gtg gaa tcg agc aaa ctg aaa gtc atg cat ttt gtg gca agg gtt 822 His Val Glu Ser Ser Lys Leu Lys Val Met His Phe Val Ala Arg Val 170 175 180 cgt aac cga tgc tct aaa gac tgg cct tgt aat tat gac tgg gat tcg 870 Arg Asn Arg Cys Ser Lys Asp Trp Pro Cys Asn Tyr Asp Trp Asp Ser 185 190 195 gac gat gat gca gag gtt gag gct atc ctc aat tca ggt gct agg ggt 918 Asp Asp Asp Ala Glu Val Glu Ala Ile Leu Asn Ser Gly Ala Arg Gly 200 205 210 215 tat tcc gcc cct taa gtagatctga ggcagaccct tgggggtgta aaagagagtc 973 Tyr Ser Ala Pro * 220 acaggtaccc caaggagtag atgccagggt cctaagttga aaatgatgtc gattgggggc 1033 gggggacact gtatttgata tttgtgatca gtgatcattg ttcaactgcg aaatagagtg 1093 tttgcttttg ataatggaaa attgtattcg ttttaaaatt ccgtttgttg agaataacaa 1153 tatgtttaaa aatataattg aacaaatttg tttctttgtt gcctgtcagg aacagttagt 1213 agaacagttt tgctagcgtt ctaaaatgaa gtcgttccat cataatctat gatcttgtac 1273 ggggggggga ggggtaagct gttcttttga agttgaaata cccagtaaaa tgttgaagaa 1333 ggatggagga tttcttcata tctgacgttt ctgaaaccct ttgtgtctgc tgttgtgtga 1393 agattgacat ttaccatgat tttccttagt tactgcagaa catagagaaa aataaaagcc 1453 taacgaataa aaaaaaaaaa a 1474 33 672 DNA Homo sapiens CDS (166)..(543) misc_feature (1)...(672) n = a,t,c or g 33 gcgcccccat cgacngcctg cggatagaac gcctgcggta ccggcccgga attcccgggt 60 cgacccacgc gtccggcagg gtgtcgccgc tgtgccgcta gcggtgcccc gcctgctgcg 120 gtggcaccag ccaggaggcg gagtggaagt ggccgtgggg cgggt atg gga cta 174 Met Gly Leu 1 gct ggc gtg tgc gcc ctg aga cgc tca gcg ggc tat ata ctc gtc ggt 222 Ala Gly Val Cys Ala Leu Arg Arg Ser Ala Gly Tyr Ile Leu Val Gly 5 10 15 ggg gcc ggc ggt cag tct gcg gca gcg gca gca aga cgg tgc agt gaa 270 Gly Ala Gly Gly Gln Ser Ala Ala Ala Ala Ala Arg Arg Cys Ser Glu 20 25 30 35 gga gag tgg gcg tct ggc ggg gtc cgc agt ttc agc aga gcc gct gca 318 Gly Glu Trp Ala Ser Gly Gly Val Arg Ser Phe Ser Arg Ala Ala Ala 40 45 50 gcc atg gcc cca atc aag gtt cgg ctc ctg gct gat ccc act ggg gcc 366 Ala Met Ala Pro Ile Lys Val Arg Leu Leu Ala Asp Pro Thr Gly Ala 55 60 65 ttt ggg aag gag aca gac tta tta cta gat gat tcg ctg gtg tcc atc 414 Phe Gly Lys Glu Thr Asp Leu Leu Leu Asp Asp Ser Leu Val Ser Ile 70 75 80 ttt ggg aat cga cgt ctc aag agg ttc tcc atg gtg gta cag gat ggc 462 Phe Gly Asn Arg Arg Leu Lys Arg Phe Ser Met Val Val Gln Asp Gly 85 90 95 ata gtg aag gcc ctg aat gtg gaa cca gat ggc aca ggc ctc acc tgc 510 Ile Val Lys Ala Leu Asn Val Glu Pro Asp Gly Thr Gly Leu Thr Cys 100 105 110 115 agc ctg gca ccc aat atc atc tca cag ctc tga ggccctgg gccagattac 561 Ser Leu Ala Pro Asn Ile Ile Ser Gln Leu * 120 125 ttcctccacc cctccctatc tcacctgccc agccctgtgc tggggccctg caattggaat 621 gttggccaga tttctgcaat aaacacttgt ggtttgcggc caaaaaaaaa a 672 34 1024 DNA Homo sapiens CDS (16)..(729) 34 gacgcgtggg cagcg atg gcg gct gcg tcg ggg tcg gtt ctg cag cgc tgt 51 Met Ala Ala Ala Ser Gly Ser Val Leu Gln Arg Cys 1 5 10 atc gtg tcg ccg gca ggg agg cat agc gcc tct ctg atc ttc ctg cat 99 Ile Val Ser Pro Ala Gly Arg His Ser Ala Ser Leu Ile Phe Leu His 15 20 25 ggc tca ggt gat tct gga caa gga tta aga atg tgg atc aag cag gtt 147 Gly Ser Gly Asp Ser Gly Gln Gly Leu Arg Met Trp Ile Lys Gln Val 30 35 40 tta aat caa gat tta aca ttc caa cac ata aaa att att tat cca aca 195 Leu Asn Gln Asp Leu Thr Phe Gln His Ile Lys Ile Ile Tyr Pro Thr 45 50 55 60 gct cct ccc aga tca tat act cct atg aaa gga gga atc tcc aat gta 243 Ala Pro Pro Arg Ser Tyr Thr Pro Met Lys Gly Gly Ile Ser Asn Val 65 70 75 tgg ttt gac aga ttt aaa ata acc aat gac tgc cca gaa cac ctt gaa 291 Trp Phe Asp Arg Phe Lys Ile Thr Asn Asp Cys Pro Glu His Leu Glu 80 85 90 tca att gat gtc atg tgt caa gtg ctt act gat ttg att gat gaa gaa 339 Ser Ile Asp Val Met Cys Gln Val Leu Thr Asp Leu Ile Asp Glu Glu 95 100 105 gta aaa agt ggc atc aag aag aac agg ata tta ata gga gga ttc tct 387 Val Lys Ser Gly Ile Lys Lys Asn Arg Ile Leu Ile Gly Gly Phe Ser 110 115 120 atg gga gga tgc atg gca atg cat tta gca tat aga aat cat caa gat 435 Met Gly Gly Cys Met Ala Met His Leu Ala Tyr Arg Asn His Gln Asp 125 130 135 140 gtg gca gga gta ttt gct ctt tct agt ttt ctg aat aaa gca tct gct 483 Val Ala Gly Val Phe Ala Leu Ser Ser Phe Leu Asn Lys Ala Ser Ala 145 150 155 gtt tac cag gct ctt cag aag agt aat ggt gta ctt cct gaa tta ttt 531 Val Tyr Gln Ala Leu Gln Lys Ser Asn Gly Val Leu Pro Glu Leu Phe 160 165 170 cag tgt cat ggt act gca gat gag tta gtt ctt cat tct tgg gca gaa 579 Gln Cys His Gly Thr Ala Asp Glu Leu Val Leu His Ser Trp Ala Glu 175 180 185 gag aca aac tca atg tta aaa tct cta gga gtg acc acg aag ttt cat 627 Glu Thr Asn Ser Met Leu Lys Ser Leu Gly Val Thr Thr Lys Phe His 190 195 200 agt ttt cca aat gtt tac cat gag cta agc aaa act gag tta gac ata 675 Ser Phe Pro Asn Val Tyr His Glu Leu Ser Lys Thr Glu Leu Asp Ile 205 210 215 220 ttg aag tta tgg att ctt aca aag ctg cca gga gaa atg gaa aaa caa 723 Leu Lys Leu Trp Ile Leu Thr Lys Leu Pro Gly Glu Met Glu Lys Gln 225 230 235 aaa tga atgaatcaag agtgatttgt taatgtaagt gtaatgtctt tgtgaaaagt 779 Lys * gatttttact gccaaattat aatgataatt aaaatattaa gaaataacac tttcctgact 839 tttttattat taaaatgctt atcactgtag acagtagcta atcttattaa tgaaaaacaa 899 tagacaaaca tctgtgcata atttttcaga cacaattctg taaatatttg gaaacctttt 959 aagtatttaa acttttaaat ttttgaaata aagtattcta aactaatata aataaggaca 1019 atgat 1024 35 1076 DNA Homo sapiens CDS (148)..(609) 35 tttgattttg cattgcagac ccaagctggc tagcgtttaa acttaagctt ggtaccgagc 60 tcggatccac tagtccagtg tggtggaatt ccagccgggc tggtcctgct gcgagccggc 120 ggcccggagt ggggcggcgg agcaaac atg aac gtt gga gtt gcc cac agt 171 Met Asn Val Gly Val Ala His Ser 1 5 gaa gtg aat cca aat acc cgt gtc atg aac agc cgg ggt atg tgg ctg 219 Glu Val Asn Pro Asn Thr Arg Val Met Asn Ser Arg Gly Met Trp Leu 10 15 20 aca tat gca ttg gga gtt ggc ttg ctt cat att gtc tta ctc agc att 267 Thr Tyr Ala Leu Gly Val Gly Leu Leu His Ile Val Leu Leu Ser Ile 25 30 35 40 ccc ttc ttc agt gtt cct gtt gct tgg act tta aca aat att ata cat 315 Pro Phe Phe Ser Val Pro Val Ala Trp Thr Leu Thr Asn Ile Ile His 45 50 55 aat ctg ggg atg tac gta ttt ttg cat gca gtg aaa gga aca cct ttc 363 Asn Leu Gly Met Tyr Val Phe Leu His Ala Val Lys Gly Thr Pro Phe 60 65 70 gaa act cct gac cag ggt aaa gca agg ctc cta act cat tgg gaa caa 411 Glu Thr Pro Asp Gln Gly Lys Ala Arg Leu Leu Thr His Trp Glu Gln 75 80 85 ctg gac tat gga gta cag ttt aca tct tca cgg aag ttt ttc aca att 459 Leu Asp Tyr Gly Val Gln Phe Thr Ser Ser Arg Lys Phe Phe Thr Ile 90 95 100 tct cca ata att cta tat ttt ctg gca agt ttc tat acg aag tat gat 507 Ser Pro Ile Ile Leu Tyr Phe Leu Ala Ser Phe Tyr Thr Lys Tyr Asp 105 110 115 120 cca act cac ttc atc cta aac aca gct tct ctc ctg agt gta cta att 555 Pro Thr His Phe Ile Leu Asn Thr Ala Ser Leu Leu Ser Val Leu Ile 125 130 135 ccc aaa atg cca caa cta cat ggt gtt cgg atc ttt gga att aat aag 603 Pro Lys Met Pro Gln Leu His Gly Val Arg Ile Phe Gly Ile Asn Lys 140 145 150 tat tga aatgttttga aactgaaaaa aaattttaca gctactgaat ttcttataag 659 Tyr * gaaggagtgg ttagtaaact gcactgtttc tgtgataatg tgaaatgaga agtatttaca 719 ttggagggcc aatggctggt ccttcaagtg ctgttttgaa gtgcagattt ccattaaatg 779 atgcctctgt ttaatacacc tggtacattt ctgaagaggg gctttataag caggctgggc 839 aggcccagct tataagttaa agggcatcac agtgagggtg tagtagataa attcaaggaa 899 ataagagatt tgtaagaaac taggaccagc ttaacttata atgaatgggc attgtgttaa 959 gaaaagaaca tttccagtca ttcagctgtg gttatttaaa gcagacttac atgtaaaccg 1019 gaatcctctc tatacaagtt tattaaagat tatttttatt accgtaaaaa aaaaaaa 1076 36 1518 DNA Homo sapiens CDS (252)..(569) 36 aaggatcctt aattaaatta atcccccccc cccccgactc ttgtttcgct ccttgacaac 60 cctggcgggg gttcgctggc tgcggccccg gctccggccc ccgcaggagc agcacccccc 120 ggggaaagac attttctgct cccaccgagt tggcagggcc tgcttcctga atctcctggg 180 tgtgtcttaa ctgccagtcc cagcacctcc tgaaagcccc actctcctcc agtggtcaca 240 gtggaaggat c atg gga gaa aca gaa ggg aag aaa gat gag gct gac tat 290 Met Gly Glu Thr Glu Gly Lys Lys Asp Glu Ala Asp Tyr 1 5 10 aag cga ctg cag acc ttc cct ctg gtc agg cac tcg gac atg cca gag 338 Lys Arg Leu Gln Thr Phe Pro Leu Val Arg His Ser Asp Met Pro Glu 15 20 25 gag atg cgc gtg gag acc atg gag cta tgt gtc aca gcc tgt gag aaa 386 Glu Met Arg Val Glu Thr Met Glu Leu Cys Val Thr Ala Cys Glu Lys 30 35 40 45 ttc tcc aac aac aac gag agc gcc gcc aag atg atc aaa gag aca atg 434 Phe Ser Asn Asn Asn Glu Ser Ala Ala Lys Met Ile Lys Glu Thr Met 50 55 60 gac aag aag ttc ggc tcc tcc tgg cac gtg gtg atc ggc gag ggc ttt 482 Asp Lys Lys Phe Gly Ser Ser Trp His Val Val Ile Gly Glu Gly Phe 65 70 75 ggg ttt gag atc acc cac gag gtg aag aac ctc ctc tac ctg tac ttc 530 Gly Phe Glu Ile Thr His Glu Val Lys Asn Leu Leu Tyr Leu Tyr Phe 80 85 90 ggg ggc acc ctg gct gtg tgc gtc tgg aag tgc tcc tga cactctgtcc 579 Gly Gly Thr Leu Ala Val Cys Val Trp Lys Cys Ser * 95 100 105 cctgccccgt cccctgcagg gccttttcct gccactcatc tggggtgggg agcagcccta 639 ggcaggtcct ggtttttcca aggagagttg gggtcttttc tttttgtctt tgtgtaccag 699 tttcctgagc cacgcccagt gtgtgaactt gacatctcca tccccaggct ctcaactgtc 759 tccctcggag tctcagggtg tggacggggc agcgggcatg ggtctgtgtg ggagacgtgg 819 ggtggggcgg tgtgacaggg tagaggaggt gggagatgag atcttccgca caggaacacg 879 ccagtccccc tttctccagg gctgccttcc ccttgcatcc tgggagcccc actgccctgc 939 catccccagt actgccggga agtgtcggcc gtccttgtca ttagtggtca tatgaaaatg 999 gccccaagaa ggagatgatt ctttcaaggg acacaggcag cttctctcct tgtcctctgg 1059 ggaggtgctg acccctcaga aaccccttcc cccaacttga ccccaggctg aacagaccac 1119 tgcatctcac tgggccagca gcccccccag cccccagcct tggtggggac caagcagcct 1179 ttcccgtccc ctcctcgacc cgtacagttg agagccaggg gctggtgtgt gggagctgct 1239 acctggcagt ttctcgaggg gtcaccgagc ctctggtggg acacctgggc aggagtgctc 1299 tcaccacgag gctgcttccg cagggaaccc tggcctgccc gcgacttcgc atcagggacc 1359 gcatgctgat ttgtactgct ctctgctggg ttttctatgt tcttttcgag tgtgggaaaa 1419 gggttttagt agaagggtga atcgtatttt acacagcggt cttatttata taaatgtctt 1479 ggtttttaca attaaaatga ccaaaaactg aaaaaaaaa 1518 37 1181 DNA Homo sapiens CDS (311)..(523) 37 cggggcggtg gattcccatg ggagccccct tatatacgac tcactatagg gaccactttg 60 tacaagaaag ctgggtacgc gtaagcttgg gcccctcgag ggatactcta gagcggccgc 120 cctgggccgg gccccaccgg acggcttgct ctgctcttta cctggggttg ctgtcgagga 180 ccctgtgcaa gactcggccg gtttttcttt ctccctgatg gacagaccca aacatagccg 240 cgcagcatcg tgaagggctg gggccttcac tcctctgtgg ctctggaaga gcccgatttc 300 ctcaggaggc atg tcg ggc ccc agg cct gtg gtg ctg agc ggg cct tcg 349 Met Ser Gly Pro Arg Pro Val Val Leu Ser Gly Pro Ser 1 5 10 gga gct ggg aag agc acc ctg ctg aag agg ctg ctc cag gag cac agc 397 Gly Ala Gly Lys Ser Thr Leu Leu Lys Arg Leu Leu Gln Glu His Ser 15 20 25 ggc atc ttt ggc ttc agc gtg tcc cat acc agg gct ctc gtg gag gga 445 Gly Ile Phe Gly Phe Ser Val Ser His Thr Arg Ala Leu Val Glu Gly 30 35 40 45 tac cac gag gaa ccc gag gcc cgg cga gga gaa cgg caa aga tta cta 493 Tyr His Glu Glu Pro Glu Ala Arg Arg Gly Glu Arg Gln Arg Leu Leu 50 55 60 ctt tgt aac cag gga ggt gat gca gcg tga c atagcagccg gcgacttcat 544 Leu Cys Asn Gln Gly Gly Asp Ala Ala * 65 70 cgagcatgcc gagttctcgg ggaacctgta tggcacgagc aaggtggcgg tgcaggccgt 604 gcaggccatg aaccgcatct gtgtgctgga cgtggacctg cagggtgtgc ggaacatcaa 664 ggccaccgat ctgcggccca tctacatctc tgtgcagccg ccttcactgc acgtgctgga 724 gcagcggctg cggcagcgca acactgaaac cgaggagagc ctggtgaagc ggctggctgc 784 tgcccaggcc gacatggaga gcagcaagga gcccggcctg tttgatgtgg tcatcattaa 844 cgacagcctg gaccaggcct acgcagagct gaaggaggcg ctctctgagg aaatcaagaa 904 agctcaaagg accggcgcct gaggcttgct gtctgttctc ggcaccccgg gcccatacag 964 gaccagggca gcagcattga gccaccccct tggcaggcga tacggcagct ctgtgccctt 1024 ggccagcatg tggagtggag gagatgctgc ccctgtggtt ggaacatcct ggggtgaccc 1084 ccgacccagc ctcgctgggc tgtcccctgt ccctatctct cactctggac ccagggctga 1144 catcctaata aaataactgt tggattagaa aaaaaaa 1181 38 556 DNA Homo sapiens CDS (151)..(504) 38 gacacagtcc gtgaattgaa tttaggtgac actatagaag agctatgacg tcgcatgcac 60 gcgtacgtag gcttggatcc tctagagcgg ccgcctacta ctactaaatt cgcggccgcg 120 tcgacgggac gttgtctgca ggcactcaga atg gtc cag cgt ttg aca tac 171 Met Val Gln Arg Leu Thr Tyr 1 5 cga cgt agg ctt tcc tac aat aca gcc tct aac aaa act agg ctg tcc 219 Arg Arg Arg Leu Ser Tyr Asn Thr Ala Ser Asn Lys Thr Arg Leu Ser 10 15 20 cga acc cct ggt aat aga att gtt tac ctt tat acc aag aag gtt ggg 267 Arg Thr Pro Gly Asn Arg Ile Val Tyr Leu Tyr Thr Lys Lys Val Gly 25 30 35 aaa gca cca aaa tct gca tgt ggt gtg tgc cca ggc aga ctt cga ggg 315 Lys Ala Pro Lys Ser Ala Cys Gly Val Cys Pro Gly Arg Leu Arg Gly 40 45 50 55 gtt cgt gct gta aga cct aaa gtt ctt atg aga ttg tcc aaa aca aag 363 Val Arg Ala Val Arg Pro Lys Val Leu Met Arg Leu Ser Lys Thr Lys 60 65 70 aaa cat gtc agc agg gcc tat ggt ggt tcc atg tgt gct aaa tgt gtt 411 Lys His Val Ser Arg Ala Tyr Gly Gly Ser Met Cys Ala Lys Cys Val 75 80 85 cgt gac agg atc aag cgt gct ttc ctt atc gag gag cag aaa atc gtt 459 Arg Asp Arg Ile Lys Arg Ala Phe Leu Ile Glu Glu Gln Lys Ile Val 90 95 100 gtg aaa gtg ttg aag gca caa gca cag agt cag aaa gct aaa taa aaa 507 Val Lys Val Leu Lys Ala Gln Ala Gln Ser Gln Lys Ala Lys * 105 110 115 aatgaaactt ttttgagtaa taaaaatgaa aagacgctgt aaaaaaaaa 556 39 3010 DNA Homo sapiens CDS (282)..(1697) 39 aaacttaagc ttggtaccga gctcggatcc actagtccag tgtggtggaa ttcccggtgc 60 gcaggcaggg caactacctg ctgtgctcac tgctgctggg caacgtgctg gtcaacacca 120 cgctcaccat cctgctcgac gacatcgccg gctcgggcct cgtggccgtg gtagtctcca 180 ccatcggtat cgtcatcttc ggagagatcg tgccccaggc catctgctcc cggcatggcc 240 tggctgtggg ggccaacacc atcttcctca ccaagttttt c atg atg atg acc 293 Met Met Met Thr 1 ttc ccc gct tcc tac ccg gtc agc aag ctg ctg gac tgc gtc ctg ggc 341 Phe Pro Ala Ser Tyr Pro Val Ser Lys Leu Leu Asp Cys Val Leu Gly 5 10 15 20 cag gag ata ggc acc gtc tat aac cgg gaa aaa ctg ctg gag atg ctc 389 Gln Glu Ile Gly Thr Val Tyr Asn Arg Glu Lys Leu Leu Glu Met Leu 25 30 35 cgg gtc acc gat ccc tac aac gac ctc gtt aag gag gag ctg aac atc 437 Arg Val Thr Asp Pro Tyr Asn Asp Leu Val Lys Glu Glu Leu Asn Ile 40 45 50 atc caa ggg gcg ctg gag ctc cgc acc aag acg gtg gag gac gtg atg 485 Ile Gln Gly Ala Leu Glu Leu Arg Thr Lys Thr Val Glu Asp Val Met 55 60 65 acc cca ctc cgg gac tgc ttc atg atc acc ggc gaa gcc atc ctg gac 533 Thr Pro Leu Arg Asp Cys Phe Met Ile Thr Gly Glu Ala Ile Leu Asp 70 75 80 ttc aac acc atg tct gag atc atg gag agc ggc tac acc cgc att cca 581 Phe Asn Thr Met Ser Glu Ile Met Glu Ser Gly Tyr Thr Arg Ile Pro 85 90 95 100 gtg ttt gaa ggg gag cgc tcc aat atc gtg gac ctg ctg ttt gtc aaa 629 Val Phe Glu Gly Glu Arg Ser Asn Ile Val Asp Leu Leu Phe Val Lys 105 110 115 gac ttg gcc ttc gtg gat ccc gat gac tgt acc ccc ctg aaa acc atc 677 Asp Leu Ala Phe Val Asp Pro Asp Asp Cys Thr Pro Leu Lys Thr Ile 120 125 130 acc aaa ttt tat aac cac ccc ttg cac ttt gtt ttc aat gac acc aag 725 Thr Lys Phe Tyr Asn His Pro Leu His Phe Val Phe Asn Asp Thr Lys 135 140 145 ttg gac gct atg ctg gaa gaa ttt aag aaa ggt aaa tct cac ctg gct 773 Leu Asp Ala Met Leu Glu Glu Phe Lys Lys Gly Lys Ser His Leu Ala 150 155 160 atc gtg cag cgg gta aac aat gag gga gaa ggg gat cca ttt tat gaa 821 Ile Val Gln Arg Val Asn Asn Glu Gly Glu Gly Asp Pro Phe Tyr Glu 165 170 175 180 gtt ctg gga atc gtc acc tta gaa gat gtg att gaa gaa atc atc aaa 869 Val Leu Gly Ile Val Thr Leu Glu Asp Val Ile Glu Glu Ile Ile Lys 185 190 195 tct gag att ctt gat gaa aca gat tta tac act gac aac aga acg aaa 917 Ser Glu Ile Leu Asp Glu Thr Asp Leu Tyr Thr Asp Asn Arg Thr Lys 200 205 210 aag aaa gtg gct cac cgg gaa cga aag caa gat ttt tct gcc ttt aag 965 Lys Lys Val Ala His Arg Glu Arg Lys Gln Asp Phe Ser Ala Phe Lys 215 220 225 cag aca gac agt gag atg aag gtt aaa ata tca cca cag ctc ctc ctg 1013 Gln Thr Asp Ser Glu Met Lys Val Lys Ile Ser Pro Gln Leu Leu Leu 230 235 240 gcc atg cac cgt ttc cta gca aca gaa gta gaa gca ttt agc cca tcc 1061 Ala Met His Arg Phe Leu Ala Thr Glu Val Glu Ala Phe Ser Pro Ser 245 250 255 260 cag atg tca gag aag atc ctt cta agg ctg cta aag cac ccc aat gtc 1109 Gln Met Ser Glu Lys Ile Leu Leu Arg Leu Leu Lys His Pro Asn Val 265 270 275 atc cag gaa ctg aaa tat gat gag aag aac aag aaa gcc ccc gaa tac 1157 Ile Gln Glu Leu Lys Tyr Asp Glu Lys Asn Lys Lys Ala Pro Glu Tyr 280 285 290 tac ctc tac cag cgc aac aag cca gta gac tac ttc gtt ctc att ctg 1205 Tyr Leu Tyr Gln Arg Asn Lys Pro Val Asp Tyr Phe Val Leu Ile Leu 295 300 305 cag ggg aaa gtg gaa gtt gaa gct ggg aaa gaa ggt atg aag ttt gaa 1253 Gln Gly Lys Val Glu Val Glu Ala Gly Lys Glu Gly Met Lys Phe Glu 310 315 320 gcg agc gcc ttc tca tac tat ggc gtg atg gcc ctg aca gcc tct cca 1301 Ala Ser Ala Phe Ser Tyr Tyr Gly Val Met Ala Leu Thr Ala Ser Pro 325 330 335 340 ggt gaa aat aag tcc cct cct cgc cca tgt ggc ttg aat cac tca gac 1349 Gly Glu Asn Lys Ser Pro Pro Arg Pro Cys Gly Leu Asn His Ser Asp 345 350 355 tct ctc agt cga agc gac cgg att gac gcc gtc aca cca aca ctg ggg 1397 Ser Leu Ser Arg Ser Asp Arg Ile Asp Ala Val Thr Pro Thr Leu Gly 360 365 370 agc agc aat aac cag ctc aat tct tcg ctc ctc caa gtc tac atc ccc 1445 Ser Ser Asn Asn Gln Leu Asn Ser Ser Leu Leu Gln Val Tyr Ile Pro 375 380 385 gat tac tcg gtg cga gcc ctt tcg gat ctg cag ttt gtt aag atc tca 1493 Asp Tyr Ser Val Arg Ala Leu Ser Asp Leu Gln Phe Val Lys Ile Ser 390 395 400 aga cag caa tac caa aat gcc ttg atg gca tcc cgg atg gac aaa acc 1541 Arg Gln Gln Tyr Gln Asn Ala Leu Met Ala Ser Arg Met Asp Lys Thr 405 410 415 420 ccc cag tct tca gac agt gaa aac act aaa atc gaa ttg act ctt acg 1589 Pro Gln Ser Ser Asp Ser Glu Asn Thr Lys Ile Glu Leu Thr Leu Thr 425 430 435 gag ctg cat gac ggg ttg cca gac gag aca gcc aac ctg ctc aac gaa 1637 Glu Leu His Asp Gly Leu Pro Asp Glu Thr Ala Asn Leu Leu Asn Glu 440 445 450 cag aac tgt gtg acg cac agt aag gcc aac cac agc ctg cac aac gaa 1685 Gln Asn Cys Val Thr His Ser Lys Ala Asn His Ser Leu His Asn Glu 455 460 465 ggc gcc atc tag gcc gcgctggctg cacccgccca ggcccgcacc cgcccagtcc 1740 Gly Ala Ile * 470 cgagggcccg gccctgtctg cccatgactt cactggtgtg agcttgtccg ccatgctgta 1800 ccctgcaaca tcctgagacc aaagaccttg tgcccttccc aggagccgcg gaggaggaca 1860 gtgagggagg aatggaaacg agagatgtga agttggcagc cggggcatgg cgttcaagat 1920 tttggagatg aactgattcc gcccaaatag aatcatgttt attttttcag ctctcccttt 1980 tatcattatt cacactcctc tgccctcgat ttgcatgaag ttgaaaattg ttgcgattta 2040 ttttttcaag agatcatgtt tttaaagtgt cttttgcaga gttttaagtt gttctgtctg 2100 aactctgctg tgatcccatg atgtgaccct gatgggctgg acttgcccct ccggtagcct 2160 tccttggccc tcccagcgag gggcaccctt cctctgtgcc ccagtgggca tcaccgtcga 2220 tctcgctggc tgaatgaaga agaccgtgtt actgcagaac ctgccaagtc tgtcatcact 2280 gtggggtgta gcctgcctca gagggacctg caatcacctc tctgagctca gtggtatttt 2340 gagaatttaa tgtttaactg tacccctttc cctcaggaag atttaacatt tgcttgggaa 2400 tgtgattttg ctcccaccct aaggaatttt tatcaccaaa atgaatgtta atgaatttaa 2460 aacccatggt ttatcattgg caagaggcaa gttgacttca tcctgtcatt ccagcctggg 2520 gtctgccagc cagccctcct ccccgaccca gcgcctaagc tcacagagtg tcgtcaccca 2580 cctccctggt ccttgctctt gttaacccaa gatgctgcta cacagatgcc aaatggaaat 2640 cttccacagg gctttttcag taaacacgtg atgtggagtg caagctcctc cccttcccac 2700 tagaacatac tttaacagaa aacgagtcgg accttctagc tgcactctgt actgtgtgcc 2760 gagaaggcat ttctagaccc gtgtttttaa aggagggaac tttggggatt gccagcccct 2820 gctcctcctc ccagggagcc aactgtccct cctcccctgt ccctgggccc atggggcccg 2880 gcagtggctg tgtcccctgc ctgagggctc tgtgcctcct gcctcagatg cggcctgtgc 2940 cagagaggct gcctgtacag ccagggtcag tttggcccca aacagggatt cagaaaccaa 3000 aaaaaaaaaa 3010 40 447 DNA Homo sapiens CDS (239)..(364) 40 atttggccct cgaggccaag aattcggcac gagactaact tcaggaacca gctcatgatc 60 tcaggatgta tggaaaaata atctttgtat tactattgtc aggagaaacg ggacaacttg 120 tccatcgttt cactgtacca gctcctgtag tgataatact cattattttg tgtgtgatgg 180 ctggtattat tggaacgatc ctcttaattt cttacagtat tcgccgactg ataaaggc 238 atg agg atg tgg cct gca tgc tgc ctg atc ttg cct aga acc gtc tgc 286 Met Arg Met Trp Pro Ala Cys Cys Leu Ile Leu Pro Arg Thr Val Cys 1 5 10 15 acc tgc tgt tct ctt gtt tat gca aac tgg ctg cac ctg cta ttc ctt 334 Thr Cys Cys Ser Leu Val Tyr Ala Asn Trp Leu His Leu Leu Phe Leu 20 25 30 tgc tta tgc ccc tac ccc tgg cta tcc taa t tccctgttct cctgcctcac 385 Cys Leu Cys Pro Tyr Pro Trp Leu Ser * 35 40 tattactgta ttctctactt ctaaataaaa ataaaacaaa atacaaaccg ttaaaaaaaa 445 aa 447 41 556 DNA Homo sapiens CDS (124)..(426) 41 cgatggcccc ccttcgaggg ctgatgtata taactatcta ttcgatgatg aagatacccc 60 accaaaccca aaaaaagaga tctctcgagg atccgaattc gcggccgcgt cgaccgagac 120 acc atg aga gcc ctc aca ctc ctc gcc cta ttg gcc ctg gcc gca ctt 168 Met Arg Ala Leu Thr Leu Leu Ala Leu Leu Ala Leu Ala Ala Leu 1 5 10 15 tgc atc gct ggc cag gca ggt gcg aag ccc agc ggt gca gag tcc agc 216 Cys Ile Ala Gly Gln Ala Gly Ala Lys Pro Ser Gly Ala Glu Ser Ser 20 25 30 aaa ggt gca gcc ttt gtg tcc aag cag gag ggc agc gag gta gtg aag 264 Lys Gly Ala Ala Phe Val Ser Lys Gln Glu Gly Ser Glu Val Val Lys 35 40 45 aga ccc agg cgc tac ctg tat caa tgg ctg gga gcc cca gtc ccc tac 312 Arg Pro Arg Arg Tyr Leu Tyr Gln Trp Leu Gly Ala Pro Val Pro Tyr 50 55 60 ccg gat ccc ctg gag ccc agg agg gag gtg tgt gag ctc aat ccg gac 360 Pro Asp Pro Leu Glu Pro Arg Arg Glu Val Cys Glu Leu Asn Pro Asp 65 70 75 tgt gac gag ttg gct gac cac atc ggc ttt cag gag gcc tat cgg cgc 408 Cys Asp Glu Leu Ala Asp His Ile Gly Phe Gln Glu Ala Tyr Arg Arg 80 85 90 95 ttc tac ggc ccg gtc tag ggtgtc gctctgctgg cctggccggc aaccccagtt 462 Phe Tyr Gly Pro Val * 100 ctgctcctct ccaggcaccc ttctttcctc ttccccttgc ccttgccctg acctcccagc 522 cctatggatg tggggtcccc atcatcccag ctgc 556 42 798 DNA Homo sapiens CDS (75)..(716) 42 taatatgact cactataggg aaagctggta cgcctgcagg taccggtccg gaattcccgg 60 gtcgacgatt tcgt atg gct gtc cca gca gtg tcc ggg ctc tcc cgg cag 110 Met Ala Val Pro Ala Val Ser Gly Leu Ser Arg Gln 1 5 10 gtg cga tgc ttc agt acc tct gtg gtc aga cca ttt gcc aag ctt gtg 158 Val Arg Cys Phe Ser Thr Ser Val Val Arg Pro Phe Ala Lys Leu Val 15 20 25 agg cct cct gtt cag gta tac ggt att gaa ggt cgc tat gcc aca gct 206 Arg Pro Pro Val Gln Val Tyr Gly Ile Glu Gly Arg Tyr Ala Thr Ala 30 35 40 ctt tat tct gct gca tca aaa cag aat aag ctg gag caa gta gaa aag 254 Leu Tyr Ser Ala Ala Ser Lys Gln Asn Lys Leu Glu Gln Val Glu Lys 45 50 55 60 gag ttg ttg aga gta gca caa atc ctg aag gaa ccc aaa gtg gct gct 302 Glu Leu Leu Arg Val Ala Gln Ile Leu Lys Glu Pro Lys Val Ala Ala 65 70 75 tct gtt ttg aat ccc tat gtg aag cgt tcc att aaa gtg aaa agc cta 350 Ser Val Leu Asn Pro Tyr Val Lys Arg Ser Ile Lys Val Lys Ser Leu 80 85 90 aat gac atc aca gca aaa gag agg ttc tct ccc ctc act acc aat ctg 398 Asn Asp Ile Thr Ala Lys Glu Arg Phe Ser Pro Leu Thr Thr Asn Leu 95 100 105 atc aat ttg ctt gct gaa aat ggt cga tta agc aat acc caa gga gtc 446 Ile Asn Leu Leu Ala Glu Asn Gly Arg Leu Ser Asn Thr Gln Gly Val 110 115 120 gtt tct gcc ttt tct acc atg atg agt gtc cat cgc gga gag gta cct 494 Val Ser Ala Phe Ser Thr Met Met Ser Val His Arg Gly Glu Val Pro 125 130 135 140 tgc aca gtg acc tct gca tct cct tta gaa gaa gcc aca ctc tct gaa 542 Cys Thr Val Thr Ser Ala Ser Pro Leu Glu Glu Ala Thr Leu Ser Glu 145 150 155 tta aaa act gtc ctc aag agc ttc cta agt caa ggc caa gta ttg aaa 590 Leu Lys Thr Val Leu Lys Ser Phe Leu Ser Gln Gly Gln Val Leu Lys 160 165 170 ttg gag gct aag act gat ccg tca atc ttg ggt gga atg att gtg cgc 638 Leu Glu Ala Lys Thr Asp Pro Ser Ile Leu Gly Gly Met Ile Val Arg 175 180 185 att ggc gag aaa tat gtt gac atg tct gtc aag acc aag att cag aag 686 Ile Gly Glu Lys Tyr Val Asp Met Ser Val Lys Thr Lys Ile Gln Lys 190 195 200 ctg ggc agg gct atg cgg gag att gtc taa a agtgttggtt ttctgccatc 737 Leu Gly Arg Ala Met Arg Glu Ile Val * 205 210 agtgaaaatt cttaaacttg gagcaacaat aaaaagcttc cagaacagaa aaaaaaaaaa 797 a 798 43 742 DNA Homo sapiens CDS (68)..(658) 43 aaggatcctt aattaaatta atcccccccc cccccccctc tttcctttcg ctgctgcggc 60 cgcagcc atg agt atg ctc agg ctt cag aag agg ctc gcc tct agt gtc 109 Met Ser Met Leu Arg Leu Gln Lys Arg Leu Ala Ser Ser Val 1 5 10 ctc cgc tgt ggc aag aag aag gtc tgg tta gac ccc aat gag acc aat 157 Leu Arg Cys Gly Lys Lys Lys Val Trp Leu Asp Pro Asn Glu Thr Asn 15 20 25 30 gaa atc gcc aat gcc aac tcc cgt cag cag atc cgg aag ctc atc aaa 205 Glu Ile Ala Asn Ala Asn Ser Arg Gln Gln Ile Arg Lys Leu Ile Lys 35 40 45 gat ggg ctg atc atc cgc aag cct gtg acg gtc cat tcc cgg gct cga 253 Asp Gly Leu Ile Ile Arg Lys Pro Val Thr Val His Ser Arg Ala Arg 50 55 60 tgc cgg aaa aac acc ttg gcc cgc cgg aag ggc agg cac atg ggc ata 301 Cys Arg Lys Asn Thr Leu Ala Arg Arg Lys Gly Arg His Met Gly Ile 65 70 75 ggt aag cgg aag ggt aca gcc aat gcc cga atg cca gag aag gtc aca 349 Gly Lys Arg Lys Gly Thr Ala Asn Ala Arg Met Pro Glu Lys Val Thr 80 85 90 tgg atg agg aga atg agg att ttg cgc cgg ctg ctc aga aga tac cgt 397 Trp Met Arg Arg Met Arg Ile Leu Arg Arg Leu Leu Arg Arg Tyr Arg 95 100 105 110 gaa tct aag aag atc gat cgc cac atg tat cac agc ctg tac ctg aag 445 Glu Ser Lys Lys Ile Asp Arg His Met Tyr His Ser Leu Tyr Leu Lys 115 120 125 gtg aag ggg aat gtg ttc aaa aac aag cgg att ctc atg gaa cac atc 493 Val Lys Gly Asn Val Phe Lys Asn Lys Arg Ile Leu Met Glu His Ile 130 135 140 cac aag ctg aag gca gac aag gcc cgc aag aag ctc ctg gct gac cag 541 His Lys Leu Lys Ala Asp Lys Ala Arg Lys Lys Leu Leu Ala Asp Gln 145 150 155 gct gag gcc cgc agg tct aag acc aag gaa gca cgc aag cgc cgt gaa 589 Ala Glu Ala Arg Arg Ser Lys Thr Lys Glu Ala Arg Lys Arg Arg Glu 160 165 170 gag cgc ctc cag gcc aag aag gag gag atc atc aag act tta tcc aag 637 Glu Arg Leu Gln Ala Lys Lys Glu Glu Ile Ile Lys Thr Leu Ser Lys 175 180 185 190 gag gaa gag acc aag aaa taa aa cctcccactt tgtctgtaca tactggcctc 690 Glu Glu Glu Thr Lys Lys * 195 tgtgattaca tagatcagcc attaaaataa aacaagcctt aaaaaaaaaa aa 742 44 440 DNA Homo sapiens CDS (188)..(337) 44 atttggccct cgaggccaag aattcggcac gagaatgctt catattaaca tagaaaagaa 60 atttcttcac ctatctcctg agtcttttga aatcttcaca tatattattt tctaaattat 120 tattatttaa aattttctta aagatggagt cttgctctgt ctcccaggct ggatagagta 180 cagtggc atg atc tta gct cac tgt aac ctc aga ctt ctg gga tca aac 229 Met Ile Leu Ala His Cys Asn Leu Arg Leu Leu Gly Ser Asn 1 5 10 aat tct ccc ctc agc ctc ctg aat agc tgg ggc tac agg tgc atg cca 277 Asn Ser Pro Leu Ser Leu Leu Asn Ser Trp Gly Tyr Arg Cys Met Pro 15 20 25 30 tca tgc atg gct aat ttt tta aaa ttt ttc gta gag atg ggg tct cgc 325 Ser Cys Met Ala Asn Phe Leu Lys Phe Phe Val Glu Met Gly Ser Arg 35 40 45 tac gta gtc tag gct gttctcaaac tcctgggctc aagcaatcct cccacctcag 380 Tyr Val Val * 50 cctcccaagg cgctgggatt ataggtgtga gtcaccatcc ctggcttcta ttttattact 440 45 1921 DNA Homo sapiens CDS (701)..(1315) 45 atgaatgcag gctgggagtc cccgctcaca gtacaggaag gtttggtgtc tggtgagggc 60 tgctctgtgc ttccaagatg gcactgggtt gttgtgtcct ctggagaggg ggaaaactgg 120 gtctcgtgtg ctcctgtggc gagcgggcgc cccggaggtt tggcaggggt agtgccaacg 180 gacacctcat ggtgtggtag cttaaactca gagcctaaac gcaggaccag ggctaggagc 240 ccaggaccag aaggcaaaac ttcctacctg atttatggat gggaacttgc agcccctgga 300 ggggaatggc ttcggtctgg agctctacgc actagttctc tgggaggaca gagggcagga 360 aaggggtgca gccaaaatca aactcggttc cacttggacg agcagtgggg agattcgctg 420 tctgaactac taaggagagt ttttaaaacc acttaccaga atctagagtg ggaattaaaa 480 tctgcgtggg cttcttcaga ttccacagaa atgaggactg ccacaccttc tccaactttt 540 gcaggctcca cccaggatgc gaaggcacta gaatttccca aattaagaac gaagaggaag 600 tttggacctt ttcggccacc gctcgcttca atatggctgc ccccagggag agacgaggct 660 accatgaagg agccgagcgc agaccctgag tccgtcaccc atg gat cgc agc gcg 715 Met Asp Arg Ser Ala 1 5 gag ttc agg aaa tgg aag gcg caa tgt ttg agc aaa gcg gac ctc agc 763 Glu Phe Arg Lys Trp Lys Ala Gln Cys Leu Ser Lys Ala Asp Leu Ser 10 15 20 cgg aag ggc agt gtt gac gag gat gtg gta gag ctt gtg cag ttt ctg 811 Arg Lys Gly Ser Val Asp Glu Asp Val Val Glu Leu Val Gln Phe Leu 25 30 35 aac atg cga gat cag ttt ttc acc acc agc tcc tgc gct ggc cgc atc 859 Asn Met Arg Asp Gln Phe Phe Thr Thr Ser Ser Cys Ala Gly Arg Ile 40 45 50 cta ctc ctt gac cgg ggt ata aat ggt ttt gag gtt cag aaa caa aac 907 Leu Leu Leu Asp Arg Gly Ile Asn Gly Phe Glu Val Gln Lys Gln Asn 55 60 65 tgt tgc tgg cta ctg gtt aca cac aaa ctt tgt gta aaa gat gat gtg 955 Cys Cys Trp Leu Leu Val Thr His Lys Leu Cys Val Lys Asp Asp Val 70 75 80 85 att gta gct ctg aag aaa gca aat ggt gat gcc act ttg aaa ttt gaa 1003 Ile Val Ala Leu Lys Lys Ala Asn Gly Asp Ala Thr Leu Lys Phe Glu 90 95 100 cca ttt gtt ctt cat gtg cag tgt cga caa ttg cag gat gca cag att 1051 Pro Phe Val Leu His Val Gln Cys Arg Gln Leu Gln Asp Ala Gln Ile 105 110 115 ctg cat tcc atg gca ata gat tct ggt ttc agg aac tct ggc ata acg 1099 Leu His Ser Met Ala Ile Asp Ser Gly Phe Arg Asn Ser Gly Ile Thr 120 125 130 gtg gga aag aga gga aaa act atg ttg gct gtc cgg agt aca cat ggc 1147 Val Gly Lys Arg Gly Lys Thr Met Leu Ala Val Arg Ser Thr His Gly 135 140 145 tta gaa gtt cca tta agc cat aag gga aaa ctg atg gtg aca gag gaa 1195 Leu Glu Val Pro Leu Ser His Lys Gly Lys Leu Met Val Thr Glu Glu 150 155 160 165 tat att gac ttc ctg tta aat gtg gca aat caa aaa atg gag gaa aac 1243 Tyr Ile Asp Phe Leu Leu Asn Val Ala Asn Gln Lys Met Glu Glu Asn 170 175 180 aag aaa aga att gag aga gat ggg gtt ttg cca tgt tgc cta ggc tgg 1291 Lys Lys Arg Ile Glu Arg Asp Gly Val Leu Pro Cys Cys Leu Gly Trp 185 190 195 tct caa act cct gga ctc aag tga ttgcccgcct tggcctccca aagtgttggg 1345 Ser Gln Thr Pro Gly Leu Lys * 200 205 attacatgca taagccaccg cacctgtctg acatatgact tgactcccaa gaaacttagg 1405 ttttacaact gcctacagca tgctttggaa agggaaacga tgactaactt acatcccaag 1465 atcaaagaga aaaataactc atcatatatt cataagaaaa aaagaaaccc agaaaaaaca 1525 cgtgcccagt gtattactaa agaaagtgat gaagaacttg aaaatgatga tgatgatgat 1585 ctaggaatca atgttaccat cttccctgaa gattactaag ctttggttct gatgtgtctt 1645 ggccgtaatg tttctagtag gttttataaa gctgctcttc ataagagtat tttagtttgt 1705 tgagtgtatc agccattcat aagccagtaa tgacaagtgc agagcttcaa actataactt 1765 tgttgcccag aggatgtgca gttgtcatct aagctctcag cagtacccgg cttatcctac 1825 gacttcacct gaaatgctat agttatccct acttttttac cagtttctcc cagaagcacc 1885 tgcttaataa atcaaagatg tttgaaaaaa aaaaaa 1921 46 1061 DNA Homo sapiens CDS (126)..(440) 46 atttggccct cgaggccaag aattcggcac gaggcggctg ccaacagatc atgagccatc 60 agctcctctg gggccagcta taggacaaca gaactctcac caaaggacca gacacagtga 120 gcacc atg gga cag tgt cgg tca gcc aac gca gag gat gct cag gaa 167 Met Gly Gln Cys Arg Ser Ala Asn Ala Glu Asp Ala Gln Glu 1 5 10 ttc agt gat gtg gag agg gcc att gag acc ctc atc aag aac ttt cac 215 Phe Ser Asp Val Glu Arg Ala Ile Glu Thr Leu Ile Lys Asn Phe His 15 20 25 30 cag tac tcc gtg gag ggt ggg aag gag acg ctg acc cct tct gag cta 263 Gln Tyr Ser Val Glu Gly Gly Lys Glu Thr Leu Thr Pro Ser Glu Leu 35 40 45 cgg gac ctg gtc acc cag cag ctg ccc cat ctc atg ccg agc aac tgt 311 Arg Asp Leu Val Thr Gln Gln Leu Pro His Leu Met Pro Ser Asn Cys 50 55 60 ggc ctg gaa gag aaa att gcc aac ctg ggc agc tgc aat gac tct aaa 359 Gly Leu Glu Glu Lys Ile Ala Asn Leu Gly Ser Cys Asn Asp Ser Lys 65 70 75 ctg gag ttc agg agt ttc tgg gag ctg att gga gaa gcg gcc aag agt 407 Leu Glu Phe Arg Ser Phe Trp Glu Leu Ile Gly Glu Ala Ala Lys Ser 80 85 90 gtg aag ctg gag agg cct gtc cgg ggg cac tga gaactccc tctggaattc 458 Val Lys Leu Glu Arg Pro Val Arg Gly His * 95 100 105 ttggggggtg ttggggagag actgtgggcc tggaaataaa acttgtctcc tctaccacca 518 ccctgtaccc tagccctgca cctgtccaca tctctgcaaa gttcagcttc cttccccagg 578 tctctgtgca ctctgtcttg gatgctctgg ggagctcatg ggtggaggag tctccaccag 638 agggaggctc aggggactgg ttgggccagg gatgaatatt tgagggataa aaattgtgta 698 agagccaaag aattggtagt agggggagaa cagagaggag ctgggctatg ggaaatgatt 758 tgaataatgg agctgggaat atggctggat atctggtact aaaaaagggt ctttaagaac 818 ctacttccta atctcttccc caatccaaac catagctgtc tgtccagtgc tctcttcctg 878 cctccagctc tgccccaggc tcctcctaga ctctgtccct gggctagggc aggggaggag 938 ggagagcagg gttgggggag aggctgagga gagtgtgaca tgtggggaga ggaccagctg 998 ggtgcttggg cattgacaga atgatggttg ttttgtatca tttgattaat aaaaaaaaaa 1058 aaa 1061 47 916 DNA Homo sapiens CDS (319)..(636) 47 tatgaaatat gccctcgagg ccaagagatt cggcacgagg gcgctctgga atcgagttac 60 gcgcgaaagg gcagagtttc tggaggaaac cgcagcctct caaccgctga ccgggtctca 120 gaaggccccc ggcaggcccg cttggcggga actgaccacg cgccagtcag gctctccagg 180 gacctgcgca ggcgcgtgtg ggcggagtcg tgcgcagggg gcggggcttc gggaaggagc 240 cacagagagg gcggggcgta ggacctgcgc ttcgggggtg gagtcggagc ggcgcggcgg 300 cggtcatgcg ggacgcgg atg cag acg cag gcg gag gcg ctg acg gcg ggg 351 Met Gln Thr Gln Ala Glu Ala Leu Thr Ala Gly 1 5 10 atg gcc ggg gtg gcc aca gct gcc gcg ggg gcg tgg aca cag ccg cag 399 Met Ala Gly Val Ala Thr Ala Ala Ala Gly Ala Trp Thr Gln Pro Gln 15 20 25 ctc cgg ccg gtg gag ctc ccc cag cgc acg cgc cag gtc cgg gca gag 447 Leu Arg Pro Val Glu Leu Pro Gln Arg Thr Arg Gln Val Arg Ala Glu 30 35 40 acg ccg cgt ctg cgc cag ggg gtc acg aat gcg gcc gca cat att cac 495 Thr Pro Arg Leu Arg Gln Gly Val Thr Asn Ala Ala Ala His Ile His 45 50 55 cct cag cgt gcc ttt ccc gac ccc ctt gga ggc gga aat cgc cca tgg 543 Pro Gln Arg Ala Phe Pro Asp Pro Leu Gly Gly Gly Asn Arg Pro Trp 60 65 70 75 gtc cct ggc acc aga tgc cga gcc cca cca aag ggt ggt tgg gaa gga 591 Val Pro Gly Thr Arg Cys Arg Ala Pro Pro Lys Gly Gly Trp Glu Gly 80 85 90 tct cac agt gag tgg cag gat cct ggt cgt ccg ctg gaa agc tga aga 639 Ser His Ser Glu Trp Gln Asp Pro Gly Arg Pro Leu Glu Ser * 95 100 105 ctgtcgcctg ctccgaattt ccgtcatcaa ctttcttgac cagctttccc tggtggtgcg 699 gaccatgcag cgctttgggc cccccgtttc ccgctaagcc tggcctgggc aaatggagcg 759 aggtcccact ttgcgtctcc ttgtaggcag tgcgtccatc cttccctagg gcaggaattc 819 ccacagttgc tactttcctg ggagggcctc atgttttatc tggttcttaa atgtttgtta 879 ctacagaaaa taaaactgcg ctactaaaaa aaaaaaa 916 48 1152 DNA Homo sapiens CDS (128)..(934) 48 atttggccct cgaggccaag aattcggcac gagcgagctg ttgtgcatcc agaggtggaa 60 ttggggcccg gcattccctc ctcgtcccgg gctggccctt gcccccaccc tgcaactcct 120 ggttgag atg ggc tca gcc aag agc gtc cca gtc aca cca gcg cgg cct 169 Met Gly Ser Ala Lys Ser Val Pro Val Thr Pro Ala Arg Pro 1 5 10 ccg ccg cac aac aag cat ctg gct cga gtg gcg gac ccc cgt tca cct 217 Pro Pro His Asn Lys His Leu Ala Arg Val Ala Asp Pro Arg Ser Pro 15 20 25 30 agt gct ggc atc ctg cgc act ccc atc cag gtg gag agc tct cca cag 265 Ser Ala Gly Ile Leu Arg Thr Pro Ile Gln Val Glu Ser Ser Pro Gln 35 40 45 cca ggc cta cca gca ggg gag caa ctg gag ggt ctt aaa cat gcc cag 313 Pro Gly Leu Pro Ala Gly Glu Gln Leu Glu Gly Leu Lys His Ala Gln 50 55 60 gac tca gat ccc cgc tct cct act ctt ggt att gca cgg aca cct atg 361 Asp Ser Asp Pro Arg Ser Pro Thr Leu Gly Ile Ala Arg Thr Pro Met 65 70 75 aag acc agc agt gga gac ccc cca agc cca ctg gtg aaa cag ctg agt 409 Lys Thr Ser Ser Gly Asp Pro Pro Ser Pro Leu Val Lys Gln Leu Ser 80 85 90 gaa gta ttt gaa act gaa gac tct aaa tca aat ctt ccc cca gag cct 457 Glu Val Phe Glu Thr Glu Asp Ser Lys Ser Asn Leu Pro Pro Glu Pro 95 100 105 110 gtt ctg ccc cca gag gca cct tta tct tct gaa ttg gac ttg cct ctg 505 Val Leu Pro Pro Glu Ala Pro Leu Ser Ser Glu Leu Asp Leu Pro Leu 115 120 125 ggt acc cag tta tct gtt gag gaa cag atg cca cct tgg aac cag act 553 Gly Thr Gln Leu Ser Val Glu Glu Gln Met Pro Pro Trp Asn Gln Thr 130 135 140 gag ttc ccc tcc aaa cag gtg ttt tcc aag gag gaa gca aga cag ccc 601 Glu Phe Pro Ser Lys Gln Val Phe Ser Lys Glu Glu Ala Arg Gln Pro 145 150 155 aca gaa acc cct gtg gcc agc cag agc tcc gac aag ccc tca agg gac 649 Thr Glu Thr Pro Val Ala Ser Gln Ser Ser Asp Lys Pro Ser Arg Asp 160 165 170 cct gag act ccc aga tct tca ggt tct atg cgc aat aga tgg aaa cca 697 Pro Glu Thr Pro Arg Ser Ser Gly Ser Met Arg Asn Arg Trp Lys Pro 175 180 185 190 aac agc agc aag gta cta ggg aga tcc ccc ctc acc atc ctg cag gat 745 Asn Ser Ser Lys Val Leu Gly Arg Ser Pro Leu Thr Ile Leu Gln Asp 195 200 205 gac aac tcc cct ggc acc ctg aca cta cga cag ggt aag cgg cct tca 793 Asp Asn Ser Pro Gly Thr Leu Thr Leu Arg Gln Gly Lys Arg Pro Ser 210 215 220 ccc cta agt gaa aat gtt agt gaa cta aag gaa gga gcc att ctt gga 841 Pro Leu Ser Glu Asn Val Ser Glu Leu Lys Glu Gly Ala Ile Leu Gly 225 230 235 act gga cga ctt ctg aaa act gga gga cga gca tgg gag caa ggc cag 889 Thr Gly Arg Leu Leu Lys Thr Gly Gly Arg Ala Trp Glu Gln Gly Gln 240 245 250 gac cat gac aag gaa aat cag cac ttt ccc ttg gtg gag agc tag gcc 937 Asp His Asp Lys Glu Asn Gln His Phe Pro Leu Val Glu Ser * 255 260 265 ctgcatggcc ccagcaatgc agtcacccag ggcctggtga tatctgtgtc ctctcacccc 997 ttctttccca gggatactga ggaatggctt gttttcttag actcctcctc agctaccaaa 1057 ctgggactca cagctttatt gggctttctt tgtgtcttgt gtgtttcttt tatattaaag 1117 gaagtaattt taaatgttac tttaaaaaaa aaaaa 1152 49 6642 DNA Homo sapiens CDS (116)..(1582) 49 ccggaattcc cgggtcgagc cacgcgtccg catctacacg aaaggcaccc cggagattgc 60 tttctgggga agcaatgctg gggtgaaaac aacacggcta gaagctcatt ctgaa atg 118 Met 1 ggg agc act gaa att ttg gaa aag gag acc cca gaa aat ctc agt aat 166 Gly Ser Thr Glu Ile Leu Glu Lys Glu Thr Pro Glu Asn Leu Ser Asn 5 10 15 ggt acc agc agc aat gtg gaa gca gcc aaa agg ttg gcc aaa cgc ctt 214 Gly Thr Ser Ser Asn Val Glu Ala Ala Lys Arg Leu Ala Lys Arg Leu 20 25 30 tat cag ctg gac aga ttc aaa aga tca gat gtt gca aaa cac ctt ggc 262 Tyr Gln Leu Asp Arg Phe Lys Arg Ser Asp Val Ala Lys His Leu Gly 35 40 45 aag aac aac gaa ttt agc aaa cta gtt gca gaa gaa tat ctg aag ttt 310 Lys Asn Asn Glu Phe Ser Lys Leu Val Ala Glu Glu Tyr Leu Lys Phe 50 55 60 65 ttt gat ttt aca gga atg acg ctg gat cag tca ctc agg tat ttc ttt 358 Phe Asp Phe Thr Gly Met Thr Leu Asp Gln Ser Leu Arg Tyr Phe Phe 70 75 80 aaa gca ttc tct ctt gtg gga gaa act caa gaa cga gag aga gtt tta 406 Lys Ala Phe Ser Leu Val Gly Glu Thr Gln Glu Arg Glu Arg Val Leu 85 90 95 ata cac ttc tcc aat aga tat ttt tat tgt aac cca gat acc att gct 454 Ile His Phe Ser Asn Arg Tyr Phe Tyr Cys Asn Pro Asp Thr Ile Ala 100 105 110 tca caa gat gga gtc cat tgc ctt acc tgt gca ata atg ctt ctt aat 502 Ser Gln Asp Gly Val His Cys Leu Thr Cys Ala Ile Met Leu Leu Asn 115 120 125 acc gat cta cat ggc cac aat att gga aag aag atg acc tgt cag gag 550 Thr Asp Leu His Gly His Asn Ile Gly Lys Lys Met Thr Cys Gln Glu 130 135 140 145 ttc att gca aat ctg caa ggg gta aat gag ggt gtt gat ttc tcc aag 598 Phe Ile Ala Asn Leu Gln Gly Val Asn Glu Gly Val Asp Phe Ser Lys 150 155 160 gat ctg ctg aaa gct ctg tac aac tca atc aag aat gag aag ctt gaa 646 Asp Leu Leu Lys Ala Leu Tyr Asn Ser Ile Lys Asn Glu Lys Leu Glu 165 170 175 tgg gca gta gat gat gaa gag aaa aaa aag tct ccc tca gaa agt act 694 Trp Ala Val Asp Asp Glu Glu Lys Lys Lys Ser Pro Ser Glu Ser Thr 180 185 190 gag gag aaa gct aac gga aca cat cca aag acc atc agt cgt att gga 742 Glu Glu Lys Ala Asn Gly Thr His Pro Lys Thr Ile Ser Arg Ile Gly 195 200 205 agt act act aac cca ttt ttg gac att cct cat gat cca aat gct gct 790 Ser Thr Thr Asn Pro Phe Leu Asp Ile Pro His Asp Pro Asn Ala Ala 210 215 220 225 gtg tac aaa agt gga ttc ttg gct cgg aaa att cat gca gat atg gat 838 Val Tyr Lys Ser Gly Phe Leu Ala Arg Lys Ile His Ala Asp Met Asp 230 235 240 gga aag aag act cca aga gga aaa cga gga tgg aaa acc ttt tat gct 886 Gly Lys Lys Thr Pro Arg Gly Lys Arg Gly Trp Lys Thr Phe Tyr Ala 245 250 255 gta ctg aag gga aca gtt ctt tac ttg caa aag gat gaa tac aag cca 934 Val Leu Lys Gly Thr Val Leu Tyr Leu Gln Lys Asp Glu Tyr Lys Pro 260 265 270 gaa aag gcc ttg tct gaa gag gac ttg aaa aac gct gtg agt gtg cac 982 Glu Lys Ala Leu Ser Glu Glu Asp Leu Lys Asn Ala Val Ser Val His 275 280 285 cac gca ttg gca tcc aag gcc acg gac tat gag aag aaa cca aac gtg 1030 His Ala Leu Ala Ser Lys Ala Thr Asp Tyr Glu Lys Lys Pro Asn Val 290 295 300 305 ttt aaa ctt aaa act gcc gac tgg agg gtc ttg ctt ttt caa act cag 1078 Phe Lys Leu Lys Thr Ala Asp Trp Arg Val Leu Leu Phe Gln Thr Gln 310 315 320 agc cca gag gaa atg caa ggg tgg ata aac aaa atc aat tgt gtg gca 1126 Ser Pro Glu Glu Met Gln Gly Trp Ile Asn Lys Ile Asn Cys Val Ala 325 330 335 gct gta ttt tct gca cca cca ttt cca gca gca atc ggc tct cag aag 1174 Ala Val Phe Ser Ala Pro Pro Phe Pro Ala Ala Ile Gly Ser Gln Lys 340 345 350 aag ttt agc cgc cca ctt ctg cct gcc act aca aca aaa ctg tct cag 1222 Lys Phe Ser Arg Pro Leu Leu Pro Ala Thr Thr Thr Lys Leu Ser Gln 355 360 365 gag gag caa ctg aag tca cat gaa agt aag ctg aag cag atc acc acc 1270 Glu Glu Gln Leu Lys Ser His Glu Ser Lys Leu Lys Gln Ile Thr Thr 370 375 380 385 gag ctg gcc gag cac cgc tca tat ccc ccc gac aag aag gtc aaa gcc 1318 Glu Leu Ala Glu His Arg Ser Tyr Pro Pro Asp Lys Lys Val Lys Ala 390 395 400 aag gac gtc gat gag tac aaa ctg aaa gac cac tat ctg gag ttt gag 1366 Lys Asp Val Asp Glu Tyr Lys Leu Lys Asp His Tyr Leu Glu Phe Glu 405 410 415 aaa acc cgc tat gaa atg tat gtc agc att ctc aag gaa gga ggc aaa 1414 Lys Thr Arg Tyr Glu Met Tyr Val Ser Ile Leu Lys Glu Gly Gly Lys 420 425 430 gag cta ctg agt aac gat gaa agc gag gct gca gga ctg aag aag tcg 1462 Glu Leu Leu Ser Asn Asp Glu Ser Glu Ala Ala Gly Leu Lys Lys Ser 435 440 445 cac tcg agt cct tcg ctg aac ccg gat act tct cca atc act gcc aaa 1510 His Ser Ser Pro Ser Leu Asn Pro Asp Thr Ser Pro Ile Thr Ala Lys 450 455 460 465 gtc aag cgt aac gtg tca gag agg aag gat cac cga cct gaa aca cca 1558 Val Lys Arg Asn Val Ser Glu Arg Lys Asp His Arg Pro Glu Thr Pro 470 475 480 agc att aag caa aaa gtt act tag agtccatctg cggccaggaa gtgctggtca 1612 Ser Ile Lys Gln Lys Val Thr * 485 tggagcaaaa tagggttttt caagatcttt ctggtaatcc gtgaatatat ttaaaaaaaa 1672 aaaagtctgt gacaaaacgg tgcattagta attttttcta ttgtatattt ttgttagttt 1732 ctgtacagat tgtctttgct cttgatttct tttgctttga tgatttttgc aacttgatag 1792 ctaatgcacc ttttctgtga ggaggagggg atcgtgattt cagaatgaat tatgtatccc 1852 ttctcttttg gttttctctt gtttgcagtc tgctcagttg ttttatgtat tctcatatca 1912 actgttaaac ttttttttaa ggttaaagaa tttaatccat tgtgaaacac ttaactggac 1972 aaactgtagt tttagtaaat tctagctgga gttaatatac gcctttatat gtgaaatctt 2032 gcccagtcac agaggtagaa ttgagcactc acagatgctc cagtaagaat cacagtgctg 2092 ggaatctagt tgctccaata tgaggcagct tcatgtgcag cttagcactt gttgttgaga 2152 tcggaccctg ctggaagcag ggaaaagaag cgtgaagatc gtaggattga gaacttaggg 2212 aagcacatta gcttgcttga agtgctgatt ccatttcagc caagcaaggg aaagaggaag 2272 tggagtcatt ttgcctttga aggctgagga aagattgata cccagttaat tttgtttgct 2332 aaaggatggg ggcaataatc ggcccttgag gagctgcagc agtaggcatg tgctcagtct 2392 gcaggaattg ttacctcact cccacagggt ctagactaga aatccatcat ctctatcgtt 2452 gatatccttc catccaggaa tagatttttc ttactctaca tatgtgtgtg tgcgtgcgtg 2512 tgtgtgcgtg tgtgggcatg gggttgtgtc ctggttgtga tattgaggtc ttccttccta 2572 acaaattaat actaaaatga aacagctttt cttgtgtcct taagacaaaa taaggaagga 2632 aaacgtagct gcagttgtcc acgatggata ttggttcttt aaaatatatc tgaaagtagt 2692 agtcagaatg aattatggtt ggaaaactga ggaatcttct ggttgcaggt gcaaagtgac 2752 tttgtttatt cttgtctcag tctccttgat agccacttca ctctgctact actcaacttt 2812 ctcctaaaaa tacttcatct attttcagtc ctttctttct gtctactcaa aatggttcta 2872 ttaactttgc agtcatgagc ttgttccagt tacagtccct ttgaagttca gggtgataaa 2932 cagaatattc ttctgtagag gaagagaaag gagtgaaagt ttagcccact gagacctaga 2992 gctttgtgat ttcctaacct tgaaactctg taatccctaa agttaaaatc tccgcaagtg 3052 gcacaacttc agaactaata gtatcacttt gatttttctt tttcctccct tagaaagttt 3112 ctctagttct atagtttatt tgttgaaggt actatgacca aagaatcagc tgctctacag 3172 gaatagcatg gttccagtga attagagaaa acctgctgta aagccatggt agtgtctaag 3232 tggtatgtta ttatgatgta ctagcattta tttacagaat tatttattaa cgtttacttc 3292 cttcccctct gtaaatgtcc atgactattg cccagagaag gcttacccct ctctagggtt 3352 gcagttgctt tctttgtaat aagtattttg ccacacctgt aaaaaaaaaa aacctcactt 3412 ttaactctct gccttgtttg ggtaaaggca gtaactaagt ttatgtttca gaactgcaaa 3472 acaaacagga tagttaccaa tatggcccat gtgtcagatt gatttttgta gcctctcact 3532 gaatccaaca tatccacaag caagttatct gtctttctac ctgataatct aaattatcag 3592 gatatttgtt ttctgcctaa atgtttatac taagccgagg ggagagaggt acctagacca 3652 tgtcatctac gagcttcagt aactaaagaa aaaggaactt ccctgagtgg cttgaatgtg 3712 tttgcccaca gtctatatct atgtatatag aatgtctgta tgtattttac ttatttaata 3772 tacattgaat ggtaccttgc tacagtattt ctgacattta gagtagtgtt gaaatactcg 3832 gctagcatca gcaccactat agcactgtcc gtgtcatatg agtcactaat attaactcca 3892 gggacttctg gataggctaa tagatcattg gatacgaagg gctcttttga agcttcagta 3952 taccatgttt gcatagttta tctttaaaaa caactttaaa ggttcttttg tgagccagga 4012 tctcagactg ccgtagcatg atgctgtcca tctttagcgc atgggctgag aacacctctt 4072 ccctgaggct tctgaaggtt gctgtctgtc atgagtgcat gaaggaggcc aagagtttat 4132 gctatgggag gaaacagtca ctgatttgcc tagattctga gagtctggcc catagccaac 4192 cacattttcc tttgggataa tttatttcct gtggcatcta gccagaagaa attgaggatg 4252 tttcctttca cagctgctcc aagcctgttg cccaattcac ggtacaaggg agcacccctt 4312 ccctttcctc tgaaggtacg ccacccacct ccgtcgccca cctcagcgcc caggagcctt 4372 gggacttcct tccatatgat aaatcattct tcttcacgtc aatacacttc atattaattt 4432 ctagtacaga aaatcttgac agctatcaga atgccttggt catagtgttg ttgcaaaatt 4492 gaccatacag gtggcccatg tataaaatct gaattttagg ggtttgtccc cacctcgcat 4552 gctggctttt acagggaggt gtctgggatt cctcattagc aatcaaaact taattactgg 4612 gatgcagagt ccttacttta tcgccagccc gtaggcattt ctgaagtgca cttttttgaa 4672 acatcatttt gctaactctc agcagtgtct aattaaactg agcaatactt ttgtgaattt 4732 taattaatct cagcaaaacc atgatgggag agagtcctct gatggaaatg tagtccctgg 4792 attatgtgta acctttttat tgctcttaga tgcagaggat agaaagcatt ttttggtgca 4852 gtggtcttgt ggcaaacaca agaccctcta tgcgtctcca actgttatcc taatctagaa 4912 aatgaggact ggcccctggg caaaagtgac atgaggaatt tactctggaa gaggaaaatc 4972 tgggtggctt tccaaggcta agataggttt gtatttcacc ctgtggccaa gctacagaac 5032 ttctgagatt gtggaagaat ttttgcaacc agcagggaaa gaggcctctt actgcctaaa 5092 cacaaagtta cactgagctt ttctactgtc ctttgcctat tgctccctct atcatgtaaa 5152 gatctgggaa ggatgagagg cagggcctgc ttgtcatgag ctgcactctt ttctttttaa 5212 ctaatcattg acaattggaa gaaaattgac gttaaagaag tttctccatt gtcttactaa 5272 caaaaccttt tgggtttcat taattgtcct tgaaattgag ttcctttggc atttttcctt 5332 gcagtcatca gttaagcatg ttgcatcctg aattcacaga agtttagctt tgcaggtttg 5392 aatctctgta atttaactcc cgtggacttg gtcgagtttt cagcaggttg ggagccacct 5452 ctcttcattt cagcagtgag tcatcccttg acttttcaaa tgacagaatt ttttccaatt 5512 gtaaaattag cactgtaaaa caaagaacca aagtggcatc ctaagagttg ttaaacctga 5572 agtctagttt atgaggaatt gtccaagttg gagtttaaat agtatctgct tttgtctcaa 5632 agcatctaag ttattctgac agaaaatggt aagtcagctt tgcaggcaga tgcgcctctg 5692 ggcctcctac cttgctccac agctttctgg ccatcttgtc tcccaggcca tgccactgct 5752 ctgccacatg tcagcaaatt tctttccacc agtcttatag catcttacat gatcaaatca 5812 tcacagaata accccgtgat agattattga tagcaataga gaggggcggc tttgtcactg 5872 atttttctct cagattcctt ttccatctct catccataaa ggaaggactg aaatccaaag 5932 gcattctcct tttgtaccta cagtatccag aacccacgtg ggcagccttc tgcttatgac 5992 aataattggc ccattgcatg cagagagaat gtcttcatag agagaatgtc attaaatact 6052 tgaatctgca tgacagtttg acttgaatgc aacagcagga aaattttgca agttacataa 6112 ttgtatatac agtaggtttt cttaagtctc ttcggttcat cctttgtaat ttgtgtgtgt 6172 atctgtagta ttgcaggctt ttggagacta ttcttacagg cagtatgtca gtcatcaaag 6232 aaaatgctgt cacctgccat tgttgtattt gtgggtattt atagttgtat gtatgtaaat 6292 gcatcagtgt gtagattgca tatcagtgta tggtacatgt acatcaaaat tatttttgtc 6352 cttaatcagt gtgatatgaa aagcaagtac aacctcatag gactgattat ataatgaagt 6412 tgttgagagt atatatagtg gtattgtttt attaaactta aactcaaata atattttgat 6472 taaaattttt aataagactt tatgctagaa aattctttga gctttgaatc accagggcaa 6532 aaatgacttt caactaacct tgtgaatctt ttgcagtgta ctgtgtgcaa taccaagggc 6592 atagctccct gtaatttggg aaatacagaa agaaaagaaa aaaaaaaaaa 6642 50 4223 DNA Homo sapiens CDS (53)..(757) 50 gatctgacgt accggtccgg aattcccggg tcgacccacg cgtccggcga aa atg 55 Met 1 gcg gct tcc agg tgg gcg cgc aag gcc gtg gtc ctg ctt tgt gcc tct 103 Ala Ala Ser Arg Trp Ala Arg Lys Ala Val Val Leu Leu Cys Ala Ser 5 10 15 gac ctg ctg ctg ctg ctg cta ctg cta cca ccg cct ggg tcc tgc gcg 151 Asp Leu Leu Leu Leu Leu Leu Leu Leu Pro Pro Pro Gly Ser Cys Ala 20 25 30 gcc gaa ggc tcg ccc ggg acg ccc gac gag tct acc cca cct ccc cgg 199 Ala Glu Gly Ser Pro Gly Thr Pro Asp Glu Ser Thr Pro Pro Pro Arg 35 40 45 aag aag aag aag gat att cgc gat tac aat gat gca gac atg gcg cgt 247 Lys Lys Lys Lys Asp Ile Arg Asp Tyr Asn Asp Ala Asp Met Ala Arg 50 55 60 65 ctt ctg gag caa tgg gag aaa gat gat gac att gaa gaa gga gat ctt 295 Leu Leu Glu Gln Trp Glu Lys Asp Asp Asp Ile Glu Glu Gly Asp Leu 70 75 80 cca gag cac aag aga cct tca gca cct gtc gac ttc tca aag ata gac 343 Pro Glu His Lys Arg Pro Ser Ala Pro Val Asp Phe Ser Lys Ile Asp 85 90 95 cca agc aag cct gaa agc ata ttg aaa atg acg aaa aaa ggg aag act 391 Pro Ser Lys Pro Glu Ser Ile Leu Lys Met Thr Lys Lys Gly Lys Thr 100 105 110 ctc atg atg ttt gtc act gta tca gga agc cct act gag aag gag aca 439 Leu Met Met Phe Val Thr Val Ser Gly Ser Pro Thr Glu Lys Glu Thr 115 120 125 gag gaa att acg agc ctc tgg cag ggc agc ctt ttc aat gcc aac tat 487 Glu Glu Ile Thr Ser Leu Trp Gln Gly Ser Leu Phe Asn Ala Asn Tyr 130 135 140 145 gac gtc cag agg ttc att gtg gga tca gac cgt gct atc ttc atg ctt 535 Asp Val Gln Arg Phe Ile Val Gly Ser Asp Arg Ala Ile Phe Met Leu 150 155 160 cgc gat ggg agc tac gcc tgg gag atc aag gac ttt ttg gtc ggt caa 583 Arg Asp Gly Ser Tyr Ala Trp Glu Ile Lys Asp Phe Leu Val Gly Gln 165 170 175 gac agg tgt gct gat gta act ctg gag ggc cag gtg tac ccc ggc aaa 631 Asp Arg Cys Ala Asp Val Thr Leu Glu Gly Gln Val Tyr Pro Gly Lys 180 185 190 gga gga gga agc aaa gag aaa aat aaa aca aag caa gac aag ggc aaa 679 Gly Gly Gly Ser Lys Glu Lys Asn Lys Thr Lys Gln Asp Lys Gly Lys 195 200 205 aaa aag aag gaa gga gat ctg aaa tct cgg tct tcc aag gaa gaa aat 727 Lys Lys Lys Glu Gly Asp Leu Lys Ser Arg Ser Ser Lys Glu Glu Asn 210 215 220 225 cga gct ggg aat aaa aga gaa gac ctg tga t ggggcagcag tgacgcgctg 778 Arg Ala Gly Asn Lys Arg Glu Asp Leu * 230 235 tggggggaca ggtggacgtg gagagctctt tgcccagctc ctggggtggg agtggtctca 838 ggcaactgca caccggatga cattctagtg tcttctagaa agggtctgcc acatgaccag 898 tttgtggtca aagaattact gcttaatagg cttcaagtaa gaagacagat gttttctaat 958 taatactgga cactgacaaa ttcatgttta ctataaaatc tccttacatg gaaatgtgac 1018 tgtgttgctt tttcccattt acacttggtg agtcatcaac tctactgaga ttccactccc 1078 ctccaagcac ctgctgtgat tgggtggcct gctctgatca gatagcaaat tctgatcaga 1138 gaagacttta aaactcttga cttaattgag taaactcttc atgccatata catcattttc 1198 attatgttaa aggtaaaata tgctttgtga actcagatgt ctgtagccag gaagccaggg 1258 tgtgtaaatc caaaatctat gcaggaaatg cggagaatag aaaatatgtc acttgaaatc 1318 ctaagtagtt ttgaatttct ttgacttgaa tcttactcat cagtaagaga actcttggtg 1378 tctgtcaggt tttatgtggt ctgtaaagtt aggggttctg ttttgtttcc ttatttagga 1438 aagagtactg ctggtgtcga ggggttatat gttccattta atgtgacagt tttaaaggat 1498 ttaagtaggg aatcagagtc ctttgcagag tgtgacagac gactcaataa cctcatttgt 1558 ttctaaacat ttttctttga taaagtgcct aaatctgtgc tttcgtatag agtaacatga 1618 tgtgctactg ttgatgtctg attttgccgt tcatgttaga gcctactgtg aataagagtt 1678 agaacattta tatacagatg tcatttctaa gaactaaaat tctttgggaa aaaccctcaa 1738 ttgtgatttt aataaattaa aagtagcaca ttacatggtt aaaaaatgtc agtgttaaag 1798 aatggtacaa agtgaaaagt gtatccctct cttgccgccg gtggtagctt gtcccagtgg 1858 aagctgctgt taacaatttg tgcccccaca tccccctccc tgcccatcca ccaaaaaaaa 1918 gtacatttac ttatgtaaat gtacttatgg tgatgtatgt ttgttttggc ctcacagcat 1978 ctgtttcccc ttaatttggt agctgctcac atttccctcg aaagaaccac accctctgca 2038 ttctcagttc tttgctttgg atgggacatt tgccctgcag tccccccacc ctccaggcca 2098 tgccctctcc agggtgaggc ctgtgtgatc taccgtacta gggtactagg ccctgaaaga 2158 ggcttttctt gttcctcttg catcttgaac ctggagcggg agctgttgta ggccccgccc 2218 ttggagaaga gaactgtctg acagtgggga gagagcgcca caccctggtg gcataaacga 2278 gtccctgaat catgccgtgg ctgaaccaag ccctgtctgt gggctttttc tgttgtactc 2338 agggcagttt gatggggtta ctgtcctgca tagccataat ggcccagtat aaagcagctg 2398 ttttgatgag ataattgctt taattaagca aaaggtagca aagctttcac tccgccctgt 2458 accttctgtt tccacttagg agccttccca tgtcagaatg tgcagatctg tctcattgtt 2518 tcctgtgcag tgtgccccca cttcacccag tagtttctgt gtgtctgtta tgtactaggt 2578 actacaaggt gccaggacgg tgtagataca gcctctgcta tcgtaaaact caatgattcg 2638 gtgggggaag acaaatgtca gtaatgtaca aagtaaaatg gcagctgtta gaagtatgaa 2698 aggggcaggg tagggggagg tagaatcttc cctgaccagg ttaagaaaac cagaggcctt 2758 ctctgagggc aagaggagga gaggagaaat agagtaaggc aggcagagga aacagtctga 2818 gctaagaccc tgtggctaga agtggcagag ggagaggcag caggaaggcc agcggggagg 2878 ctggggccca gtgcaggccc aggttggagg agcgtagcac atggagtttg gtaggagttt 2938 gggacgccct ggtggatctt aattgtgatg gggtgggtgt gaaaggcagt ccaggttgca 2998 ctggttgcac aggagaagtg atcagaagag gaccccagca ggtgtgagcc gtgagctggg 3058 aggtgcttca gtagtgcagg ccatagctga aggtgtccta catcagcagg gtgatggtga 3118 ggtttgaacc actgtttcac tgcatagtcc ctgctgatgg acacttgagt gttcagattt 3178 tttgctggta tattcagtgc tgcagtggac attttcatac aaaatatttc ggtacacttt 3238 tgtttatatc tgaaaggtaa attcctagca gtagaattat tagagcaaac ggaatttaac 3298 attttggtgt gtattgccaa attgccctcc caagtggttt agtcagctta cccttgccaa 3358 caatagatct atccttgcca gccttgggca tcacatttac cagtttaata gattgtaaaa 3418 ccatatctta attggctacc ctgaagccac catactggag aggctgcgta cagtgtttca 3478 cgtagagaga gggataccca ggaggcccac ctgctccaac cccagctgca tgagtcttcc 3538 cagcccaggc acagacatgt ggataagatt taaacatttc cagccccagc cttcaagcaa 3598 tcctagttga cactgagggg agccaacata agctgagctg agaaacagtc tgcccagtct 3658 gcagattcat gagcaaaaga aatgttgggc tgggtacagt ggctcacgcc tgtaatccca 3718 gtactttggg aggccgaggt gggtggatca gttgaggtca ggagtttgag accagcctgg 3778 ccaacatggt gaagccctgt ctctactaaa aattagccga gtgtggtggt gcgggcctgt 3838 aatcccagct actcaggtgg ctgaggcagg agaatggctt gaacccggga ggcggaggtt 3898 gcagtgagcc aagatcaggc cactgcactc cagcctggat gacgggatga gactctgtct 3958 caaaaaaacg aaacaaaaat tttttaagag aaatgtcatt tgtttttgtt tttgagacag 4018 ggtctcactc tgttgccctc actagagtgc agtagggatc acggctcact gaagtctcta 4078 cctaccggct caattgatct tcccaccaca gcctcccaaa tagctgggag aaatgtcctg 4138 tttttaatga atttgtcttc ctttttgtct tgtttgtttt aatatctagt gatctaataa 4198 atttggatga tatcttttga ctatc 4223 51 996 DNA Homo sapiens CDS (179)..(613) 51 ttgatatacg gagatccaag ctggctagcg tttaaactta agcttggtac cgagctcgga 60 tccactagtc cagtgtggtg gaattcgcgg gctgtctcgg aaactcagag ccgggttcct 120 cccgggtttc tgccgggttt ctccctgcgg ctcctgggtt gttgagactc ttgtgaag 178 atg gct tgc gct gcc gcg cgg tcc ccg gcc gac cag gac agg ttt att 226 Met Ala Cys Ala Ala Ala Arg Ser Pro Ala Asp Gln Asp Arg Phe Ile 1 5 10 15 tgt atc tat cct gct tat tta aat aat aag aag acc atc gca gag gga 274 Cys Ile Tyr Pro Ala Tyr Leu Asn Asn Lys Lys Thr Ile Ala Glu Gly 20 25 30 agg cga atc ccc ata agt aag gct gtt gaa aat cct aca gct aca gag 322 Arg Arg Ile Pro Ile Ser Lys Ala Val Glu Asn Pro Thr Ala Thr Glu 35 40 45 att caa gat gta tgt tca gca gtt gga ctt aac gta ttt ctt gag aaa 370 Ile Gln Asp Val Cys Ser Ala Val Gly Leu Asn Val Phe Leu Glu Lys 50 55 60 aat aaa atg tac tct aga gaa tgg aat cgt gat gtc caa tac aga ggc 418 Asn Lys Met Tyr Ser Arg Glu Trp Asn Arg Asp Val Gln Tyr Arg Gly 65 70 75 80 aga gtc cgg gtc cag ctc aaa cag gaa gat ggg agc ctc tgc ctt gta 466 Arg Val Arg Val Gln Leu Lys Gln Glu Asp Gly Ser Leu Cys Leu Val 85 90 95 cag ttc cca tca cgt aag tca gta atg ttg tat gca gca gaa atg ata 514 Gln Phe Pro Ser Arg Lys Ser Val Met Leu Tyr Ala Ala Glu Met Ile 100 105 110 cct aaa cta aaa aca agg aca caa aaa aca gga ggt gct gac caa agt 562 Pro Lys Leu Lys Thr Arg Thr Gln Lys Thr Gly Gly Ala Asp Gln Ser 115 120 125 ctt caa caa gga gag gga agt aaa aaa ggg aaa gga aag aaa aag aag 610 Leu Gln Gln Gly Glu Gly Ser Lys Lys Gly Lys Gly Lys Lys Lys Lys 130 135 140 taa ccta gtatcagcat caagtatgtg gtactactgt aagagacatg aatggagact 667 * 145 tctaatttgt atcggaggga aacagaagct ttttgtttgc atcatttaac tgaactgtga 727 acccttgtgc ctctcatctt tatcatcgga gttgacagtg aaacaaattt acatcagaag 787 tttgcatctc gcgtatatgc cgtataaaag aatttttttg tctttcaatg cagttttttg 847 gaagaaaata tttttaaatg gacaatggac tgtacaataa gttacttgaa ataagttgtt 907 tcagataaat ttcaattaga tttaaaataa acattatgtc caccttttaa gttaatgaaa 967 taaaatttga aactgacaaa aaaaaaaaa 996 52 2346 DNA Homo sapiens CDS (86)..(1564) 52 tctgacgacg caattcggca cgagggtggc gctggcggtt gctgtcagct gattcccggg 60 gttggtggca gcggcggtag cagca atg gac ttt ctc ctg ggg aac ccg ttc 112 Met Asp Phe Leu Leu Gly Asn Pro Phe 1 5 agc tct cca gtg gga cag cgc atc gag aaa gcc aca gat ggc tcc ctg 160 Ser Ser Pro Val Gly Gln Arg Ile Glu Lys Ala Thr Asp Gly Ser Leu 10 15 20 25 cag agc gag gac tgg gcc ctc aac atg gag atc tgc gac atc atc aac 208 Gln Ser Glu Asp Trp Ala Leu Asn Met Glu Ile Cys Asp Ile Ile Asn 30 35 40 gag acg gag gaa ggt ccc aaa gat gcc ctc cga gca gta aag aag aga 256 Glu Thr Glu Glu Gly Pro Lys Asp Ala Leu Arg Ala Val Lys Lys Arg 45 50 55 atc gtg ggg aat aag aac ttc cac gag gtg atg ctg gct ctc aca gtc 304 Ile Val Gly Asn Lys Asn Phe His Glu Val Met Leu Ala Leu Thr Val 60 65 70 tta gaa acc tgt gtc aag aac tgc ggg cac cgc ttc cac gtg ctg gtg 352 Leu Glu Thr Cys Val Lys Asn Cys Gly His Arg Phe His Val Leu Val 75 80 85 gcc agc cag gac ttc gtg gag agt gtg ctg gtg agg acc atc ctg ccc 400 Ala Ser Gln Asp Phe Val Glu Ser Val Leu Val Arg Thr Ile Leu Pro 90 95 100 105 aag aac aac cca ccc acc atc gtg cat gac aaa gtg ctc aac ctc atc 448 Lys Asn Asn Pro Pro Thr Ile Val His Asp Lys Val Leu Asn Leu Ile 110 115 120 cag tcc tgg gct gac gcg ttc cgc agc tcg ccc gat ctg aca ggt gtg 496 Gln Ser Trp Ala Asp Ala Phe Arg Ser Ser Pro Asp Leu Thr Gly Val 125 130 135 gtc acc atc tat gag gac ctg cgg agg aaa ggc ctg gag ttc ccc atg 544 Val Thr Ile Tyr Glu Asp Leu Arg Arg Lys Gly Leu Glu Phe Pro Met 140 145 150 act gac ctg gac atg ctg tca ccc atc cac aca ccc cag agg acc gtg 592 Thr Asp Leu Asp Met Leu Ser Pro Ile His Thr Pro Gln Arg Thr Val 155 160 165 ttc aac tca gag aca caa tca gga cag gat tct gtg ggc act gac tcc 640 Phe Asn Ser Glu Thr Gln Ser Gly Gln Asp Ser Val Gly Thr Asp Ser 170 175 180 185 agc cag caa gag gac tct ggc cag cat gct gcc cct ctg ccc gcc ccg 688 Ser Gln Gln Glu Asp Ser Gly Gln His Ala Ala Pro Leu Pro Ala Pro 190 195 200 ccc ata ctc tcc ggt gac acg ccc ata gca cca acc ccg gaa cag att 736 Pro Ile Leu Ser Gly Asp Thr Pro Ile Ala Pro Thr Pro Glu Gln Ile 205 210 215 ggg aag ctg cgc agt gag ctg gag atg gtg agt ggg aac gtg agg gtg 784 Gly Lys Leu Arg Ser Glu Leu Glu Met Val Ser Gly Asn Val Arg Val 220 225 230 atg tcg gag atg ctg acg gag ctg gtg ccc acc cag gcc gag ccc gca 832 Met Ser Glu Met Leu Thr Glu Leu Val Pro Thr Gln Ala Glu Pro Ala 235 240 245 gac ctg gag ctg ctg cag gag ctc aac cgc acg tgc cga gcc atg cag 880 Asp Leu Glu Leu Leu Gln Glu Leu Asn Arg Thr Cys Arg Ala Met Gln 250 255 260 265 cag cgg gtc ctg gag ctc atc cct cag atc gcc aat gag cag ctg aca 928 Gln Arg Val Leu Glu Leu Ile Pro Gln Ile Ala Asn Glu Gln Leu Thr 270 275 280 gag gag ctg ctc atc gtc aat gac aat ctc aac aat gtg ttc ctg cgc 976 Glu Glu Leu Leu Ile Val Asn Asp Asn Leu Asn Asn Val Phe Leu Arg 285 290 295 cat gaa cgg ttt gaa cgg ttc cga aca ggc cag acc acc aag gcc cca 1024 His Glu Arg Phe Glu Arg Phe Arg Thr Gly Gln Thr Thr Lys Ala Pro 300 305 310 agt gag gcc gag ccg gca gct gac ctg atc gac atg ggc cct gac cca 1072 Ser Glu Ala Glu Pro Ala Ala Asp Leu Ile Asp Met Gly Pro Asp Pro 315 320 325 gca gcc acc ggc aac ctc tca tcc cag ctg gca gga atg aac ctg ggc 1120 Ala Ala Thr Gly Asn Leu Ser Ser Gln Leu Ala Gly Met Asn Leu Gly 330 335 340 345 tcc agc agt gtg aga gct ggc ctg cag tct ctg gag gcc tct ggt cga 1168 Ser Ser Ser Val Arg Ala Gly Leu Gln Ser Leu Glu Ala Ser Gly Arg 350 355 360 ctg gaa gat gag ttt gac atg ttt gcg ctg aca cgg ggc agc tca ctg 1216 Leu Glu Asp Glu Phe Asp Met Phe Ala Leu Thr Arg Gly Ser Ser Leu 365 370 375 gct gac caa cgg aaa gag gta aaa tac gaa gcc ccc caa gca aca gac 1264 Ala Asp Gln Arg Lys Glu Val Lys Tyr Glu Ala Pro Gln Ala Thr Asp 380 385 390 ggc ctg gct gga gcc ctg gac gcc cgg cag cag agc act ggc gcg atc 1312 Gly Leu Ala Gly Ala Leu Asp Ala Arg Gln Gln Ser Thr Gly Ala Ile 395 400 405 cca gtc acc cag gcc tgc ctc atg gag gac atc gag cag tgg ctg tcc 1360 Pro Val Thr Gln Ala Cys Leu Met Glu Asp Ile Glu Gln Trp Leu Ser 410 415 420 425 act gac gtg ggt aat gat gcg gaa gag cct aag ggg gtc acc agc gaa 1408 Thr Asp Val Gly Asn Asp Ala Glu Glu Pro Lys Gly Val Thr Ser Glu 430 435 440 gaa ttt gac aaa ttc ctg gaa gaa cgg gcc aaa gcc gcg gac cga ttg 1456 Glu Phe Asp Lys Phe Leu Glu Glu Arg Ala Lys Ala Ala Asp Arg Leu 445 450 455 ccc aac ctc tcc agc ccc tca gct gag ggg ccc ccg ggt ccc cca tct 1504 Pro Asn Leu Ser Ser Pro Ser Ala Glu Gly Pro Pro Gly Pro Pro Ser 460 465 470 ggc cca gcg ccc cgg aag aag acc cag gag aaa gat gat gac atg ctg 1552 Gly Pro Ala Pro Arg Lys Lys Thr Gln Glu Lys Asp Asp Asp Met Leu 475 480 485 ttt gcc tta tga gtg tggggtctgg caccctgcag cccaggtccc cactgctctc 1607 Phe Ala Leu * 490 acacccttag gctgggacct ccctccctcc tctggtgtta aggctgcttt gggggtggct 1667 tgttaccccc ttttcctcct ctttgaagac ggagctgccc cagctgtggc tgggggtgtg 1727 gaggcagtgg gatgaactgg gggacaggtc tgcgctgcag tgggatctgg ctgctctgcc 1787 tcctttccca ccccagctga ccatgagact ttgctgagaa gtggaggccc caggacaggc 1847 tggctggctg gctggctgct tgacccagtg tgactctcct tcactgagtg ataccctgct 1907 ccgggcccat gccccaagga gcccttcaga gcccacactg ccagtcgagg cctggctgga 1967 ggctggccac agtggaaatt ctgccgagcc tcttgtccct tccctgctct gctgcatggg 2027 gccccatggc tttggctggc cactgagggt agggtgtgga ggtgtggagg ccccctgagg 2087 agctgcggcg gcccaggtac gaagctgcaa ctctgcgcgc agtgggcgag atctcatcag 2147 ccccaggctg caggtgaggc ttcaggggat gctgggcccc actgcccctc cgctgccttg 2207 ccctccatcc ttcctctgtt ccttctggcc gggcaccaca gcactggggc tcacctcttg 2267 gttgatcctc ttgtactggg agaggtgcct tttgtatccc caattaaagg tagaaaacca 2327 ccctgctaaa aaaaaaaaa 2346 53 866 DNA Homo sapiens CDS (313)..(492) 53 aagtattgaa atgtcttttt aaaattttaa ccaccgtatt tattggttca aaaactagaa 60 tttatagttt caggcagatt tcaaccaaag agtcaccaaa ttaaatacac agggtagctt 120 gtgaggcata gacacagccc atgtgttttc ctctacattg tatattcatt tctctttggc 180 gatttgacat tatagccatt ctctggaagt cctaaagcaa actagtattt tatgtgccat 240 attaagttaa aatttcttat gtgagatacc actaatactg gttttgattt aggccatcct 300 tcttgcctgg at atg aca atg gag ctt gtt tct atg att aag acc tac 348 Met Thr Met Glu Leu Val Ser Met Ile Lys Thr Tyr 1 5 10 cca tgg cag tgt atg gaa tgt aaa aca tgc att ata tgt gga caa ccc 396 Pro Trp Gln Cys Met Glu Cys Lys Thr Cys Ile Ile Cys Gly Gln Pro 15 20 25 cac cat gaa gaa gaa atg atg ttc tgt gat atg tgt gac aga ggt tat 444 His His Glu Glu Glu Met Met Phe Cys Asp Met Cys Asp Arg Gly Tyr 30 35 40 cat act ttt tgt gtg ggc ctt ggt gct att cca tca ggt aaa gat taa 492 His Thr Phe Cys Val Gly Leu Gly Ala Ile Pro Ser Gly Lys Asp * 45 50 55 60 aaaaagagca aacattatct ttgggtgatg agactctccc agcactccaa aaggctgcat 552 aaacgctatc atgacatgaa gagcttgtgg actcttatgt gcaaatatga ccaaagctgt 612 gattatacag gtcatgtcca ccagcttttc atccctagac aattccaact aaaggataag 672 tgaaaggcca gaatgcccct gctaagtttt ggaagtatag ttctatagaa tgagctggtg 732 tttttctact gaaatactaa agtaacaaag gaattccacc acactggact agtggatccg 792 agctcggtac caagcttaag tttaaacgct agccagctgg gtctccgtat accaaagtct 852 ccgtatatcc aagg 866 54 537 DNA Homo sapiens CDS (208)..(324) 54 aattagtttc agtggcttga ttctaggcca agattctggc aacagattgt agtcttacct 60 tgttttcttc aatctcactg gatctctctc tctttttacc ccccttaggc tgagggtaaa 120 aagctgggat tggtaggctg ggtccagaac actgaccggg gcacagtgca aggacaattg 180 caaggtccca tctccaaggt gcgtcat atg cag gaa tgg ctt gaa aca aga 231 Met Gln Glu Trp Leu Glu Thr Arg 1 5 gga agt cct aaa tca cac atc gac aaa gca aac ttc aac aat gaa aaa 279 Gly Ser Pro Lys Ser His Ile Asp Lys Ala Asn Phe Asn Asn Glu Lys 10 15 20 gtc atc ttg aag ttg gat tac tca gac ttc caa att gta aaa taa tgg 327 Val Ile Leu Lys Leu Asp Tyr Ser Asp Phe Gln Ile Val Lys * 25 30 35 cctgaattta agttttctaa gataaactca gtggtttggt ttttattatt aatagagata 387 gaactattgt gtgttaatgt tagcattagt caataagtta ttttaatgtc agatttttga 447 atgttattat atattacctg tatgatggaa ggattaccac tgtacacaaa tctaatcaat 507 aaaaacgtta gaaccttcaa aaaaaaaaaa 537 55 613 DNA Homo sapiens CDS (201)..(416) 55 ttcttgttaa agccaaaaaa actttccaga cagaataaaa cataaatcaa actatatgcc 60 caagagccac atctgaaaca ggctggacgc aaaatgatga aagacacatt ggtcaaattc 120 caaccaaatg actatcatat gaagtacact ttgttttatc tcatttttat tattcttatc 180 ttttatatat attttttgag atg gag tct cac tct gtc acc cag gct gca 230 Met Glu Ser His Ser Val Thr Gln Ala Ala 1 5 10 gtg cag tgg cac cat ctc ggc tca ctg caa cct ctg cct ccc ggg ttc 278 Val Gln Trp His His Leu Gly Ser Leu Gln Pro Leu Pro Pro Gly Phe 15 20 25 aag caa ttc tct gcc tca gcc tgc cga gta gct ggg att aca gat gcc 326 Lys Gln Phe Ser Ala Ser Ala Cys Arg Val Ala Gly Ile Thr Asp Ala 30 35 40 cgc cac cat gcc tgg cta att ttt gta ttt tta gta gag acg ggg ttt 374 Arg His His Ala Trp Leu Ile Phe Val Phe Leu Val Glu Thr Gly Phe 45 50 55 cac cat ctt ggg cag tct ggt ctt gaa ctc ctg atc tca tga tccaccc 423 His His Leu Gly Gln Ser Gly Leu Glu Leu Leu Ile Ser * 60 65 70 gccttggcct ccctaagtgc tgggattaca ggcatgagcc accacaccca gccatgaagt 483 ataggtcgac cggccgcgaa tttagtagta gtaggcggcc gctctagagg atccaagctt 543 acgtacgcgt gcatgcgacg tcatagctct tctatagtgt cacctaaatt caattcactg 603 gccgtcgtag 613 56 2993 DNA Homo sapiens CDS (1)..(1644) 56 atg atc gct gat gat aag cca gct gcg atg gct ggt gag tca gct gga 48 Met Ile Ala Asp Asp Lys Pro Ala Ala Met Ala Gly Glu Ser Ala Gly 1 5 10 15 ag tca tct gag tct gga gtt ggg gcc aac ttc ttt ggc atc aca ttc 96 ln Ser Ser Glu Ser Gly Val Gly Ala Asn Phe Phe Gly Ile Thr Phe 20 25 30 ag aca aca gaa aca ctg atg agc aca ggg cat ctg aat ggg gcc gaa 144 ln Thr Thr Glu Thr Leu Met Ser Thr Gly His Leu Asn Gly Ala Glu 35 40 45 gc aaa gca ggt cca ggc act gtg aag acc ctg gcg gtg gag gaa gag 192 ys Lys Ala Gly Pro Gly Thr Val Lys Thr Leu Ala Val Glu Glu Glu 50 55 60 ct tcc cgg ctg tgg agg aag cca gac cct tac aac aca aga cga gaa 240 la Ser Arg Leu Trp Arg Lys Pro Asp Pro Tyr Asn Thr Arg Arg Glu 65 70 75 80 ca gac ctg cgt ggg gga gct ctg gat gct aca ggg gct caa gga ggg 288 ro Asp Leu Arg Gly Gly Ala Leu Asp Ala Thr Gly Ala Gln Gly Gly 85 90 95 ca ctg gac cga gcg cgc aaa gaa cct gag acc gct tgc tct cac cgc 336 ro Leu Asp Arg Ala Arg Lys Glu Pro Glu Thr Ala Cys Ser His Arg 100 105 110 gc aag tcg gtc gca gga cag aca cca gtg ggc agc aac aaa aaa aga 384 rg Lys Ser Val Ala Gly Gln Thr Pro Val Gly Ser Asn Lys Lys Arg 115 120 125 ac cgg gtt ccg gga cac gtg ccg gcg gct gga cta acc tca gcg gct 432 sn Arg Val Pro Gly His Val Pro Ala Ala Gly Leu Thr Ser Ala Ala 130 135 140 ca acc aag gag cgc gca caa tgc tcc gat aca ggg ggt ctg gat ccc 480 la Thr Lys Glu Arg Ala Gln Cys Ser Asp Thr Gly Gly Leu Asp Pro 145 150 155 160 ac tct gcg ggc cat ttc tcc aga gcg act ttg ctc ttc tgt cct ccc 528 yr Ser Ala Gly His Phe Ser Arg Ala Thr Leu Leu Phe Cys Pro Pro 165 170 175 ac act cac cgc tgc atc tcc ctc acc aaa agc gag aag tcg gag cga 576 is Thr His Arg Cys Ile Ser Leu Thr Lys Ser Glu Lys Ser Glu Arg 180 185 190 aa cag ctc ttt ctg ccc aag ccc cag tca gct gtt ttc ggg tcc gag 624 ln Gln Leu Phe Leu Pro Lys Pro Gln Ser Ala Val Phe Gly Ser Glu 195 200 205 ga agg agg acc ctg cga aag ctg cga cga cta tct tcc cct ggg gcc 672 ly Arg Arg Thr Leu Arg Lys Leu Arg Arg Leu Ser Ser Pro Gly Ala 210 215 220 tg gac tcg gac gcc agc ctg gtg tcc agc cgc ccg tcg tcg cca gag 720 et Asp Ser Asp Ala Ser Leu Val Ser Ser Arg Pro Ser Ser Pro Glu 225 230 235 240 cc gat gac ctt ttt ctg ccg gcc cgg agt aag ggc agc agc ggc agc 768 ro Asp Asp Leu Phe Leu Pro Ala Arg Ser Lys Gly Ser Ser Gly Ser 245 250 255 cc ttc act ggg ggc acc gtg tcc tcg tcc acc ccg agt gac tgc ccg 816 la Phe Thr Gly Gly Thr Val Ser Ser Ser Thr Pro Ser Asp Cys Pro 260 265 270 cg gag ctg agc gcc gag ctg cgc ggc gct atg ggc tct gcg ggc gcg 864 ro Glu Leu Ser Ala Glu Leu Arg Gly Ala Met Gly Ser Ala Gly Ala 275 280 285 at cct ggg gac aag cta gga ggc agt ggc ttc aag tca tcc tcg tcc 912 is Pro Gly Asp Lys Leu Gly Gly Ser Gly Phe Lys Ser Ser Ser Ser 290 295 300 gc acc tcg tcg tct acg tcg tcg gcg gct gcg tcg tcc acc aag aag 960 er Thr Ser Ser Ser Thr Ser Ser Ala Ala Ala Ser Ser Thr Lys Lys 305 310 315 320 ac aag aag caa atg aca gag ccg gag ctg cag cag ctg cgt ctc aag 1008 sp Lys Lys Gln Met Thr Glu Pro Glu Leu Gln Gln Leu Arg Leu Lys 325 330 335 tc aac agc cgc gag cgc aag cgc atg cac gac ctc aac atc gcc atg 1056 le Asn Ser Arg Glu Arg Lys Arg Met His Asp Leu Asn Ile Ala Met 340 345 350 at ggc ctc cgc gag gtc atg ccg tac gca cac ggc cct tcg gtg cgc 1104 sp Gly Leu Arg Glu Val Met Pro Tyr Ala His Gly Pro Ser Val Arg 355 360 365 ag ctt tcc aag atc gcc acg ctg ctg ctg gcg cgc aac tac atc ctc 1152 ys Leu Ser Lys Ile Ala Thr Leu Leu Leu Ala Arg Asn Tyr Ile Leu 370 375 380 tg ctc acc aac tcg ctg gag gag atg aag cga ctg gtg agc gag atc 1200 et Leu Thr Asn Ser Leu Glu Glu Met Lys Arg Leu Val Ser Glu Ile 385 390 395 400 ac ggg ggc cac cac gct ggc ttc cac ccg tcg gcc tgc ggc ggc ctg 1248 yr Gly Gly His His Ala Gly Phe His Pro Ser Ala Cys Gly Gly Leu 405 410 415 cg cac tcc gcg ccc ctg ccc gcc gcc acc gcg cac ccg gca gca gca 1296 la His Ser Ala Pro Leu Pro Ala Ala Thr Ala His Pro Ala Ala Ala 420 425 430 cg cac gcc gca cat cac ccc gcg gtg cac cac ccc atc ctg ccg ccc 1344 la His Ala Ala His His Pro Ala Val His His Pro Ile Leu Pro Pro 435 440 445 cc gcc gca gcg gct gct gcc gcc gct gca gcc gcg gct gtg tcc agc 1392 la Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Ala Val Ser Ser 450 455 460 cc tct ctg ccc gga tcc ggg ctg ccg tcg gtc ggc tcc atc cgt cca 1440 la Ser Leu Pro Gly Ser Gly Leu Pro Ser Val Gly Ser Ile Arg Pro 465 470 475 480 cg cac ggc cta ctc aag tct ccg tct gct gcc gcg gcc gcc ccg ctg 1488 ro His Gly Leu Leu Lys Ser Pro Ser Ala Ala Ala Ala Ala Pro Leu 485 490 495 gg ggc ggg ggc ggc ggc agt ggg gcg agc ggg ggc ttc cag cac tgg 1536 ly Gly Gly Gly Gly Gly Ser Gly Ala Ser Gly Gly Phe Gln His Trp 500 505 510 gc ggc atg ccc tgc ccc tgc agc atg tgc cag gtg ccg ccg ccg cac 1584 ly Gly Met Pro Cys Pro Cys Ser Met Cys Gln Val Pro Pro Pro His 515 520 525 ac cac gtg tcg gct atg ggc gcc ggc agc ctg ccg cgc ctc acc tcc 1632 is His Val Ser Ala Met Gly Ala Gly Ser Leu Pro Arg Leu Thr Ser 530 535 540 ac gcc aag tga gcc tactggcgcc ggcgcgttct ggcgacaggg gagccagggg 1687 sp Ala Lys * 545 cgcggggaa gcgaggactg gcctgcgctg ggctcgggag ctctgtcgcg aggaggggcg 1747 aggaccatg gactgggggt ggggcatggt ggggattcca gcatctgcga acccaagcaa 1807 gggggcgcc cacagagcag tggggagtga ggggatgttc tctccgggac ctgatcgagc 1867 ctgtctggc tttaacctga gctggtccag tagacatcgt tttatgaaaa ggtaccgctg 1927 gtgcattcc tcactagaac tcatccgacc cccgaccccc acctccggga aaagattcta 1987 aaacttctt tccctgagag cgtggcctga cttgcagact cggcttgggc agcacttcgg 2047 gggggaggg ggttttatgg gagggggaca cattggggcc ttgctcctct tcctcctttc 2107 tggcgggtg ggagactccg ggtagccgca ctgcagaagc aacagcccga ccgcgccctc 2167 agggtcgtc cctggcccaa ggccaggggc cacaagttag ttggaagccg gcgttcggta 2227 cagaagcgc tgatggtcat atccaatctc aatatctggg tcaatccaca ccctcttaga 2287 ctgtggccg ttcctccctg tctctcgttg atttgggaga atatggtttt ctaataaatc 2347 gtggatgtt ccttcttcaa cagtatgagc aagtttatag acattcagag tagaaccact 2407 gtggattgg aataacccaa aactgccgat ttcaggggcg ggtgcattgt agttattatt 2467 taaaataga aactacccca ccgactcatc tttccttctc taagcacaaa gtgatttggt 2527 attttggta cctgagaacg taacagaatt aaaaggcagt tgctgtggaa acagtttggg 2587 tatttgggg gttctgttgg ctttttaaaa ttttcttttt tggatgtgta aatttatcaa 2647 gatgaggta agtgcgcaat gctaagctgt ttgctcacgt gactgccagc cccatcggag 2707 ctaagccgg ctttcctcta ttttggttta tttttgccac gtttaacaca aatggtaaac 2767 cctccacgt gcttcctgcg ttccgtgcaa gccgcctcgg cgctgcctgc gttgcaaact 2827 ggctttgta gcgtctgccg tgtaacaccc ttcctctgat cgcaccgccc ctcgcagaga 2887 tgtatcatc tgttttattt ttgtaaaaac aaagtgctaa ataatattta ttacttgttt 2947 gttgcaaaa acggaataaa tgactgagtg ttgagatttt aaaaaa 2993 57 866 DNA Homo sapiens CDS (310)..(513) 57 cccggtcgac ccacgcgtcc gcggacgcgt ggggcaatat atacactatt atatacccac 60 aaaaaataaa aataaaggct gggtgccatg gctcacacct gtaatcccac cacttcagga 120 ggcctgaggt cgggagtttg agaccaacct ggccaacatg gagaaaccac gtctctactg 180 aaaatacaaa atcagctggg catggtggta catgcctata atcccagcta ctcgggaggc 240 tgaggcagga caatcgcctg aaccctggag gtggaggcta cggtgagccg agatcgtgct 300 gagagcaag atg ggt cac cag cag ctg tac tgg agc cac ccg cga aaa 348 Met Gly His Gln Gln Leu Tyr Trp Ser His Pro Arg Lys 1 5 10 ttc ggc cag ggt tct cgc tct tgt cgt gtc tgt tca aac cgg cac ggt 396 Phe Gly Gln Gly Ser Arg Ser Cys Arg Val Cys Ser Asn Arg His Gly 15 20 25 ctg atc cgg aaa tat ggc ctc aat atg tgc cgc cag tgt ttc cgt cag 444 Leu Ile Arg Lys Tyr Gly Leu Asn Met Cys Arg Gln Cys Phe Arg Gln 30 35 40 45 tac gcg aag gat atc ggt ttc att aag aaa gac ctg agc tgt ctt cct 492 Tyr Ala Lys Asp Ile Gly Phe Ile Lys Lys Asp Leu Ser Cys Leu Pro 50 55 60 tgg cac tgc cta tgg agg tga ca cccatctcct ccatcatggc catcctgaga 545 Trp His Cys Leu Trp Arg * 65 ccgctcgcga agcccaagat catcaaaaag agcaccaagt tcactgggaa ccagtcagac 605 tgatatgtca aaattaaggg taactggtgg aaacacagag gtattgacaa cagggttcat 665 agaaggtttg agggccagat ctatgcccaa cattggttat gggagaaaca aaaagacaaa 725 gcacatactg cccagtggct tctggaagtt cctggtccac aacgttaagg agctggaagt 785 actgctggtg agcaacaaat cttactgtgt tgagatcact catgatgttt cttccaagaa 845 ctgcaaagcc atcttggaaa g 866 58 676 DNA Homo sapiens CDS (175)..(399) 58 atttggccct cgagcagcaa attcggcacg aggagcggct ggagaggtgg tcggagaagt 60 aggaacctcc tgccgggctc gtggcggctt ctgtccgctc cgcgagggaa gcgccttccc 120 cacaggacat caatgcaagc ttgaataaga aaaacaaatt cttcctccta agcc atg 177 Met 1 gca tat cag tta tac aga aat act act ttg gga aac agt ctt cag gag 225 Ala Tyr Gln Leu Tyr Arg Asn Thr Thr Leu Gly Asn Ser Leu Gln Glu 5 10 15 agc cta gat gag ctc ata cag ggc tct cta aat acg tac aga ttc tgc 273 Ser Leu Asp Glu Leu Ile Gln Gly Ser Leu Asn Thr Tyr Arg Phe Cys 20 25 30 gat aat gtg tgg act ttt gta ctg aat gat gtt gaa ttc aga gag gtg 321 Asp Asn Val Trp Thr Phe Val Leu Asn Asp Val Glu Phe Arg Glu Val 35 40 45 aca gaa ctt att aaa gtg gat aaa gtg aaa att gta gcc tgt gat ggt 369 Thr Glu Leu Ile Lys Val Asp Lys Val Lys Ile Val Ala Cys Asp Gly 50 55 60 65 aaa aat act ggc tcc aat act aca gaa tga a tagaaaaaat atgacttttt 420 Lys Asn Thr Gly Ser Asn Thr Thr Glu * 70 75 tacaccatct tctgttattc attgcttttg aagagaagca tagaagagac tttttattta 480 ttctagaatt gcagaaatga ctacactgtg ctataccaga gaattccagt agaaagaaac 540 ttgtaactct gtagcctctt acatcacctt tattatacag catgaaaaac cataactttt 600 ttttaaggac aaaagttgtt gccttcctaa gaaccttctt taataaactc attttaaaac 660 tctgaaaaaa aaaaaa 676 59 1960 DNA Homo sapiens CDS (563)..(1069) 59 tatagggaat ttggccctcg aggccaagaa ttcggcacga ggctatgcgc ggcttcccgg 60 cgctcgtgga atcttctgga gcccttttct ccactcagcg agcctgagag tgcggaagtc 120 tccggctggt ggggcatggc ccaggagcac tagtgatgat gcgggtgtgc tggttggtga 180 gacaggacag ccggcaccag cgaatcagac ttccacattt ggaagcagtt gtgattgggc 240 gtggcccaga gaccaagatc actgataaga aatgttctcg acagcaagta cagttgaaag 300 cagagtgtaa caagggatat gtcaaggtaa agcagagttt gaggaagagg caaagaaccc 360 tggcctggaa acacacagga agagaaagag atcaggcaac agtgattcta tagaaaggga 420 tgctgctcag gaagctgagg ctgggacagg gctggaacct gggagcaact ctggccaatg 480 ctctgtgccc ctaaagaagg gaaaagatgc acctatcaaa aaggaatccc tgggccactg 540 gagtcaaggc ttgaagattt ct atg cag gac ccc aaa atg cag gtt tac aaa 592 Met Gln Asp Pro Lys Met Gln Val Tyr Lys 1 5 10 gat gag cag gtg gtg gtg ata aag gat aaa tac cca aag gcc cgt tac 640 Asp Glu Gln Val Val Val Ile Lys Asp Lys Tyr Pro Lys Ala Arg Tyr 15 20 25 cat tgg ctg gtc tta ccg tgg acc tcc att tcc agt ctg aag gct gtg 688 His Trp Leu Val Leu Pro Trp Thr Ser Ile Ser Ser Leu Lys Ala Val 30 35 40 gcc agg gaa cac ctt gaa ctc ctt aag cat atg cac act gtg ggg gaa 736 Ala Arg Glu His Leu Glu Leu Leu Lys His Met His Thr Val Gly Glu 45 50 55 aag gtg att gta gat ttt gct ggg tcc agc aaa ctc cgc ttc cga ttg 784 Lys Val Ile Val Asp Phe Ala Gly Ser Ser Lys Leu Arg Phe Arg Leu 60 65 70 ggc tac cac gcc att ccg agt atg agc cat gta cat ctt cat gtg atc 832 Gly Tyr His Ala Ile Pro Ser Met Ser His Val His Leu His Val Ile 75 80 85 90 agc cag gat ttt gat tct cct tgc ctt aaa aac aaa aaa cat tgg aat 880 Ser Gln Asp Phe Asp Ser Pro Cys Leu Lys Asn Lys Lys His Trp Asn 95 100 105 tct ttc aat aca gaa tac ttc cta gaa tca caa gct gtg atc gag atg 928 Ser Phe Asn Thr Glu Tyr Phe Leu Glu Ser Gln Ala Val Ile Glu Met 110 115 120 gta caa gag gct ggt aga gta act gtc cga gat ggg atg cct gag ctc 976 Val Gln Glu Ala Gly Arg Val Thr Val Arg Asp Gly Met Pro Glu Leu 125 130 135 ttg aag ctg ccc ctt cgt tgt cat gag tgc cag cag ctg ctg cct tcc 1024 Leu Lys Leu Pro Leu Arg Cys His Glu Cys Gln Gln Leu Leu Pro Ser 140 145 150 att cct cag ctg aaa gaa cat ctc agg aag cac tgg aca cag tga ttc 1072 Ile Pro Gln Leu Lys Glu His Leu Arg Lys His Trp Thr Gln * 155 160 165 tgcagagcct gagctgctgc tgtggtgtgg cccactggag caaactgctg gcacctattc 1132 tgggttgctt gtgaacttct actcatttcc taaattaaaa catgcagctt tttcacaaat 1192 ttattctatt attgagtggc cacaatgtag agtggctcaa agtacttcag gattaggaat 1252 ttgggtttgt catagatgta ttctctggtg agggtggctg ggatatacct gacccaccat 1312 cttcagaagg acccatgtca ggtctgacca ttgggagcaa agccatgttc acactgacct 1372 aatgcagagt atggaagcat tgggctggtt atacatttct gtttcttaga tttatcctcc 1432 gcctctgtag gcatggacaa cctttaatca gagcatctag agtggcctct tgtttatcct 1492 gaagatactg atgggtcttg ttttctgtta gtctgttttg taatattctt ttcccttcct 1552 tcatggggag gcttagtttg tccagtcctt ccatgccctt ctatcccaga ttacctaaat 1612 gttcccttct caggaattct gtctcatcag ttcttcacag tgagaaaaga ggctagatga 1672 tggtgtgggg ggttggagtt ttcttctaat accgagggtt cctggctgtg aggaaacagc 1732 cacatgttcg tcatgattga gctgtgaagt cttcttggac ctgttgtctg aaaataaagt 1792 taatttgttt gaggcatctc tcttaagtag gtggaaacta ttgaagttca gctaacaatc 1852 acagcatagg ttctgatgca tggaaaggtg gttggtgaat gaaaaagttg cgtagagcca 1912 ctactttctt tttccctgag aataaatttg gataaaacaa aaaaaaaa 1960 60 454 DNA Homo sapiens CDS (50)..(346) 60 ttccggccgc gtcgacgcat cctgtccagc aaagaagcaa tcagccaaa atg ata 55 Met Ile 1 cct gga ggc tta tct gag gcc aaa ccc gcc act cca gaa atc cag gag 103 Pro Gly Gly Leu Ser Glu Ala Lys Pro Ala Thr Pro Glu Ile Gln Glu 5 10 15 att gtt gat aag gtt aaa cca cag ctt gaa gaa aaa aca aat gag act 151 Ile Val Asp Lys Val Lys Pro Gln Leu Glu Glu Lys Thr Asn Glu Thr 20 25 30 tac gga aaa ttg gaa gct gtg cag tat aaa act caa gtt gtt gct gga 199 Tyr Gly Lys Leu Glu Ala Val Gln Tyr Lys Thr Gln Val Val Ala Gly 35 40 45 50 aca aat tac tac att aag gta cga gca ggt gat aat aaa tat atg cac 247 Thr Asn Tyr Tyr Ile Lys Val Arg Ala Gly Asp Asn Lys Tyr Met His 55 60 65 ttg aaa gta ttc aaa agt ctt ccc gga caa aat gag gac ttg gta ctt 295 Leu Lys Val Phe Lys Ser Leu Pro Gly Gln Asn Glu Asp Leu Val Leu 70 75 80 act gga tac cag gtt gac aaa aac aag gat gac gag ctg acg ggc ttt 343 Thr Gly Tyr Gln Val Asp Lys Asn Lys Asp Asp Glu Leu Thr Gly Phe 85 90 95 tag cagc atgtacccaa agtgttctga ttccttcaac tggctactga gtcatgatcc 400 * ttgctgataa atataaccat caataaagaa gcattctttt ccaaaaaaaa aaaa 454 61 5826 DNA Homo sapiens CDS (351)..(3677) misc_feature (1)...(5826) n = a,t,c or g 61 gcggggcact ttgaagaatc acgtgtgttg aggccctctt aaagagatag gcacctactt 60 ttccctccac cctaaacacc gccctgaggg cggcggcgac cgtggtaatt gcaactgctc 120 aggggcaggg cttgccccag cgccgagtag tggcaacggc gtggttgcgt cgggggtgcc 180 tgggagcctg gagtcccggg ggcctgaaat cggcagcttc ccgggcagac actctctccc 240 tcaggaagag gtgccgccga gtcagcgcgg ggcagtgtga gcgccccgag gtgctttctc 300 agttgaggag aggtggggtt acagggcaca ggtgacaggg ccggagaaag atg gag 356 Met Glu 1 cag ccc ggg gcg gcg gcg tcg gga gcg gga ggc ggc agc gag gaa ccc 404 Gln Pro Gly Ala Ala Ala Ser Gly Ala Gly Gly Gly Ser Glu Glu Pro 5 10 15 ggt ggg ggc cgg agc aac aag cgg agc gcg ggg aac cgg gcc gcc aat 452 Gly Gly Gly Arg Ser Asn Lys Arg Ser Ala Gly Asn Arg Ala Ala Asn 20 25 30 gaa gag gaa acg aaa aac aaa ccc aaa ttg aac att caa ata aaa act 500 Glu Glu Glu Thr Lys Asn Lys Pro Lys Leu Asn Ile Gln Ile Lys Thr 35 40 45 50 ttg gca gat gat gtg cgt gac cga att aca agt ttt aga aaa tct act 548 Leu Ala Asp Asp Val Arg Asp Arg Ile Thr Ser Phe Arg Lys Ser Thr 55 60 65 gtc aaa aaa gaa aaa cct ctt att caa cat cct att gat tct caa gtc 596 Val Lys Lys Glu Lys Pro Leu Ile Gln His Pro Ile Asp Ser Gln Val 70 75 80 gcg atg agt gag ttt cct gca gct cag cca tta tat gat gaa cga tct 644 Ala Met Ser Glu Phe Pro Ala Ala Gln Pro Leu Tyr Asp Glu Arg Ser 85 90 95 ttg aat ttg tca gaa aag gaa gta ttg gat ctc ttt gaa aaa atg atg 692 Leu Asn Leu Ser Glu Lys Glu Val Leu Asp Leu Phe Glu Lys Met Met 100 105 110 gag gac atg aac ctt aac gaa gag aaa aaa gct cct tta cga aac aaa 740 Glu Asp Met Asn Leu Asn Glu Glu Lys Lys Ala Pro Leu Arg Asn Lys 115 120 125 130 gac ttt acc acc aaa cgt gag atg gtt gtc cag tat att tct gcc act 788 Asp Phe Thr Thr Lys Arg Glu Met Val Val Gln Tyr Ile Ser Ala Thr 135 140 145 gcc aaa tct ata gtt gga agt aaa gtt acg ggt ggg ctg aaa aac agc 836 Ala Lys Ser Ile Val Gly Ser Lys Val Thr Gly Gly Leu Lys Asn Ser 150 155 160 aaa cat gaa tgc acc ctg tct tca caa gaa tat gtt cat gaa tta cga 884 Lys His Glu Cys Thr Leu Ser Ser Gln Glu Tyr Val His Glu Leu Arg 165 170 175 tcg ggt ata tca gat gag aaa ctt ctt aat tgc cta gaa tcc ctc agg 932 Ser Gly Ile Ser Asp Glu Lys Leu Leu Asn Cys Leu Glu Ser Leu Arg 180 185 190 gtt tct tta acc agc aat ccg gtc agc tgg gtt aac aac ttt ggc cat 980 Val Ser Leu Thr Ser Asn Pro Val Ser Trp Val Asn Asn Phe Gly His 195 200 205 210 gaa ggt ctt gga ctc tta ttg gat gag ctg gaa aag ctt ctg gac aaa 1028 Glu Gly Leu Gly Leu Leu Leu Asp Glu Leu Glu Lys Leu Leu Asp Lys 215 220 225 aaa cag caa gaa aat att gac aag aag aat cag tat aaa ctt att caa 1076 Lys Gln Gln Glu Asn Ile Asp Lys Lys Asn Gln Tyr Lys Leu Ile Gln 230 235 240 tgc ctc aaa gca ttt atg aat aat aag ttt gga tta caa agg att cta 1124 Cys Leu Lys Ala Phe Met Asn Asn Lys Phe Gly Leu Gln Arg Ile Leu 245 250 255 gga gat gaa aga agt ctt tta cta ttg gca aga gca att gac ccc aaa 1172 Gly Asp Glu Arg Ser Leu Leu Leu Leu Ala Arg Ala Ile Asp Pro Lys 260 265 270 caa ccc aac atg atg act gaa ata gta aaa ata ctt tct gct att tgc 1220 Gln Pro Asn Met Met Thr Glu Ile Val Lys Ile Leu Ser Ala Ile Cys 275 280 285 290 att gtt gga gaa gag aac att cta gat aaa ctt tta ggg gct ata aca 1268 Ile Val Gly Glu Glu Asn Ile Leu Asp Lys Leu Leu Gly Ala Ile Thr 295 300 305 aca gca gca gaa aga aat aac agg gaa cga ttt tca cca att gtg gaa 1316 Thr Ala Ala Glu Arg Asn Asn Arg Glu Arg Phe Ser Pro Ile Val Glu 310 315 320 ggt tta gaa aat cag gaa gcc ttg caa tta cag gtg gcc tgc atg cag 1364 Gly Leu Glu Asn Gln Glu Ala Leu Gln Leu Gln Val Ala Cys Met Gln 325 330 335 ttt ata aat gcc ctt gtc act tct cct tat gag ctt gat ttt cga ata 1412 Phe Ile Asn Ala Leu Val Thr Ser Pro Tyr Glu Leu Asp Phe Arg Ile 340 345 350 cat tta agg aat gaa ttc ctc cgt tca gga cta aaa aca atg tta cca 1460 His Leu Arg Asn Glu Phe Leu Arg Ser Gly Leu Lys Thr Met Leu Pro 355 360 365 370 gat cta aaa gaa aaa gag aat gat gag ctt gat att cag ttg aaa gta 1508 Asp Leu Lys Glu Lys Glu Asn Asp Glu Leu Asp Ile Gln Leu Lys Val 375 380 385 ttt gat gaa aac aaa gaa gat gac cta act gaa tta tca cac cgt ctc 1556 Phe Asp Glu Asn Lys Glu Asp Asp Leu Thr Glu Leu Ser His Arg Leu 390 395 400 aat gac att cga gca gaa atg gat gat atg aat gaa gtc tac cat ctt 1604 Asn Asp Ile Arg Ala Glu Met Asp Asp Met Asn Glu Val Tyr His Leu 405 410 415 cta tat aat atg ctg aag gac act gct gct gaa aat tac ttc tta tct 1652 Leu Tyr Asn Met Leu Lys Asp Thr Ala Ala Glu Asn Tyr Phe Leu Ser 420 425 430 att cta caa cat ttt ttg ctt atc aga aat gat tat tat atc agg cca 1700 Ile Leu Gln His Phe Leu Leu Ile Arg Asn Asp Tyr Tyr Ile Arg Pro 435 440 445 450 caa tat tat aaa ata att gag gaa tgt gtt tca cag ata gtg cta cac 1748 Gln Tyr Tyr Lys Ile Ile Glu Glu Cys Val Ser Gln Ile Val Leu His 455 460 465 tgc agt ggt atg gat cca gac ttc aaa tac agg caa aga tta gac atc 1796 Cys Ser Gly Met Asp Pro Asp Phe Lys Tyr Arg Gln Arg Leu Asp Ile 470 475 480 gat tta act cat ctg ata gat tct tgt gtg aac aag gcg aaa gtt gaa 1844 Asp Leu Thr His Leu Ile Asp Ser Cys Val Asn Lys Ala Lys Val Glu 485 490 495 gaa agt gaa caa aaa gct gca gag ttt tca aag aag ttc gat gaa gaa 1892 Glu Ser Glu Gln Lys Ala Ala Glu Phe Ser Lys Lys Phe Asp Glu Glu 500 505 510 ttc aca gct cga cag gaa gct caa gca gag ctt caa aaa aga gat gag 1940 Phe Thr Ala Arg Gln Glu Ala Gln Ala Glu Leu Gln Lys Arg Asp Glu 515 520 525 530 aaa atc aaa gaa ctt gaa gca gaa atc cag caa ctt cga acc cag gca 1988 Lys Ile Lys Glu Leu Glu Ala Glu Ile Gln Gln Leu Arg Thr Gln Ala 535 540 545 caa gta ctc tca agt tca tca gga att cca ggt cct cct gca gca cct 2036 Gln Val Leu Ser Ser Ser Ser Gly Ile Pro Gly Pro Pro Ala Ala Pro 550 555 560 cca ttg cca ggt gta ggg ccg cct cca cca cca ccc gcg cca cct cta 2084 Pro Leu Pro Gly Val Gly Pro Pro Pro Pro Pro Pro Ala Pro Pro Leu 565 570 575 ccc gga gga gct cct ctt cct cct cca cca cct cct tta cct gga atg 2132 Pro Gly Gly Ala Pro Leu Pro Pro Pro Pro Pro Pro Leu Pro Gly Met 580 585 590 atg ggg ata cca cca cca ccc cca cca cca ctt tta ttt ggg gga cct 2180 Met Gly Ile Pro Pro Pro Pro Pro Pro Pro Leu Leu Phe Gly Gly Pro 595 600 605 610 cct cca cca cca ccc ctt gga gga gtt cct cct ccc cca gga ata tca 2228 Pro Pro Pro Pro Pro Leu Gly Gly Val Pro Pro Pro Pro Gly Ile Ser 615 620 625 ctt aat cta cct tat gga atg aag cag aaa aaa atg tat aaa cct gaa 2276 Leu Asn Leu Pro Tyr Gly Met Lys Gln Lys Lys Met Tyr Lys Pro Glu 630 635 640 gtg tcc atg aag aga atc aat tgg tca aag att gaa ccc aca gaa tta 2324 Val Ser Met Lys Arg Ile Asn Trp Ser Lys Ile Glu Pro Thr Glu Leu 645 650 655 tct gag aac tgt ttc tgg tta aga gtc aaa gaa gac aag ttt gag aat 2372 Ser Glu Asn Cys Phe Trp Leu Arg Val Lys Glu Asp Lys Phe Glu Asn 660 665 670 cca gat ctc ttt gcc aaa ttg gca ttg aat ttt gct act cag ata aaa 2420 Pro Asp Leu Phe Ala Lys Leu Ala Leu Asn Phe Ala Thr Gln Ile Lys 675 680 685 690 gtt caa aag aac gca gaa gca tta gaa gaa aag aag act ggg cct aca 2468 Val Gln Lys Asn Ala Glu Ala Leu Glu Glu Lys Lys Thr Gly Pro Thr 695 700 705 aag aag aaa gtg aaa gaa ctg aga att ttg gat ccc aaa aca gct cag 2516 Lys Lys Lys Val Lys Glu Leu Arg Ile Leu Asp Pro Lys Thr Ala Gln 710 715 720 aat ctg tcc atc ttt ctg gga tca tat cgc atg cca tat gaa gac ata 2564 Asn Leu Ser Ile Phe Leu Gly Ser Tyr Arg Met Pro Tyr Glu Asp Ile 725 730 735 aga aac gtt att ctg gag gtt aat gaa gac atg ctg agt gag gct tta 2612 Arg Asn Val Ile Leu Glu Val Asn Glu Asp Met Leu Ser Glu Ala Leu 740 745 750 att cag aac ctt gtg aaa cat ctt cct gag cag aag ata ctc aac gaa 2660 Ile Gln Asn Leu Val Lys His Leu Pro Glu Gln Lys Ile Leu Asn Glu 755 760 765 770 tta gca gag ctt aag aat gaa tat gat gac ctc tgt gag cct gaa caa 2708 Leu Ala Glu Leu Lys Asn Glu Tyr Asp Asp Leu Cys Glu Pro Glu Gln 775 780 785 ttt gga gtt gtg atg agc tct gtg aaa atg tta cag cct cgt ctc agt 2756 Phe Gly Val Val Met Ser Ser Val Lys Met Leu Gln Pro Arg Leu Ser 790 795 800 agt atc ctg ttc aag ctc aca ttt gaa gaa cac ata aac aac atc aaa 2804 Ser Ile Leu Phe Lys Leu Thr Phe Glu Glu His Ile Asn Asn Ile Lys 805 810 815 cca agc atc ata gca gta act ctt gcc tgt gaa gaa ctg aag aaa agt 2852 Pro Ser Ile Ile Ala Val Thr Leu Ala Cys Glu Glu Leu Lys Lys Ser 820 825 830 gaa agc ttt aac aga ctt tta gag tta gtt ctt ctt gtt gga aac tac 2900 Glu Ser Phe Asn Arg Leu Leu Glu Leu Val Leu Leu Val Gly Asn Tyr 835 840 845 850 atg aac tca ggc tca aga aat gcc cag tct ttg gga ttt aag atc aac 2948 Met Asn Ser Gly Ser Arg Asn Ala Gln Ser Leu Gly Phe Lys Ile Asn 855 860 865 ttc ctt tgt aag atc aga gat act aaa tca gcg gat caa aaa aca acc 2996 Phe Leu Cys Lys Ile Arg Asp Thr Lys Ser Ala Asp Gln Lys Thr Thr 870 875 880 ctt ttg cat ttt att gcc gac att tgt gag gaa aaa tat cga gat atc 3044 Leu Leu His Phe Ile Ala Asp Ile Cys Glu Glu Lys Tyr Arg Asp Ile 885 890 895 cta aaa ttt cct gaa gaa ctg gaa cac gta gaa agt gca agc aaa gtt 3092 Leu Lys Phe Pro Glu Glu Leu Glu His Val Glu Ser Ala Ser Lys Val 900 905 910 tca gct caa att ctc aag agc aac ctt gca tca atg gaa caa caa att 3140 Ser Ala Gln Ile Leu Lys Ser Asn Leu Ala Ser Met Glu Gln Gln Ile 915 920 925 930 gtt cat ctg gaa cgt gac atc aag aaa ttc ccc caa gca gaa aat caa 3188 Val His Leu Glu Arg Asp Ile Lys Lys Phe Pro Gln Ala Glu Asn Gln 935 940 945 cac gat aag ttt gtg gaa aag atg acc agc ttt aca aag act gcc cga 3236 His Asp Lys Phe Val Glu Lys Met Thr Ser Phe Thr Lys Thr Ala Arg 950 955 960 gaa cag tat gaa aaa ctc tcc acc atg cac aac aac atg atg aag ctc 3284 Glu Gln Tyr Glu Lys Leu Ser Thr Met His Asn Asn Met Met Lys Leu 965 970 975 tat gag aat ctt gga gaa tac ttc att ttt gac tca aag aca gtg agc 3332 Tyr Glu Asn Leu Gly Glu Tyr Phe Ile Phe Asp Ser Lys Thr Val Ser 980 985 990 ata gaa gag ttc ttt ggt gat ctc aac aac ttc cga act ttg ttt ttg 3380 Ile Glu Glu Phe Phe Gly Asp Leu Asn Asn Phe Arg Thr Leu Phe Leu 995 1000 1005 1010 gaa gca gtg aga gaa aac aat aag aga aga gaa atg gaa gag aag acc 3428 Glu Ala Val Arg Glu Asn Asn Lys Arg Arg Glu Met Glu Glu Lys Thr 1015 1020 1025 agg agg gca aaa ctt gca aaa gag aaa gct gaa caa gaa aag tta gaa 3476 Arg Arg Ala Lys Leu Ala Lys Glu Lys Ala Glu Gln Glu Lys Leu Glu 1030 1035 1040 cgc cag aag aaa aag aaa caa ctc att gat ata aac aaa gag ggt gat 3524 Arg Gln Lys Lys Lys Lys Gln Leu Ile Asp Ile Asn Lys Glu Gly Asp 1045 1050 1055 gag act ggt gtg atg gat aat ctt cta gaa gcc cta caa tca ggt gca 3572 Glu Thr Gly Val Met Asp Asn Leu Leu Glu Ala Leu Gln Ser Gly Ala 1060 1065 1070 gca ttc aga gac cgt cga aag cgg att cca agg aat cca gat aac aga 3620 Ala Phe Arg Asp Arg Arg Lys Arg Ile Pro Arg Asn Pro Asp Asn Arg 1075 1080 1085 1090 cga gta cct ttg gaa agg tca cgc tct cgc cac aat gga gct atc tca 3668 Arg Val Pro Leu Glu Arg Ser Arg Ser Arg His Asn Gly Ala Ile Ser 1095 1100 1105 tct aag tga ttcctga tgccaaagaa tatgaaaata tttaagtaaa aacaaaatga 3724 Ser Lys * tgcattttga gaagaacaaa gtgtgcactc agcggctgga aaggaaataa gtgcatttct 3784 gcaaagatca agataagctg gatgaagtag tgtgcatttg taatactatt gcaagactcc 3844 tcccacaatt attctaatct gaacacagtt atcaggatta caaaatgtgt tccattttag 3904 tgtaaagatg tgtatcattt gtaattgtgt gtgacctgac tgtgatgatg gaagtgtaag 3964 aaattgaaga gttctaaggc tttcaaaaac actcagtcaa aaatttaaaa tcttaaatgt 4024 gtaagtcacc cccaccaaaa acaaaagaga agaaaaagaa tagaaagaat tatccagtgt 4084 cagcttccaa tccctagtac atatataata gaaaagggcc aagaaaaata tgcatcttga 4144 tttggagaga ggctaatatt atgcacactg taagagaagc cattttggaa attcacgaaa 4204 gtactgctcc accccagttg agttatttag aattttatct caagtgaaag ctgatggatt 4264 catctgcttt ggctgaaatt aaacttatca ttagtctagc tagcatttca gcatgatatt 4324 gcaagcactt ctcattgcta aaaataaata aaccaaagtt taaccgaatc agttagggaa 4384 agtgatttaa actttattta aagaggtatt ttctaattat gcacagatat ctactttata 4444 caaatacttt atatggctat ttttgagaaa accctcacat tttaatgttt atgctaggga 4504 tgaacctgaa aattctatta cgtttattta gatttcaaag gcaaatattg attcctatgc 4564 tctgtggttt atttcttttt tctattgctt ctttctccct tgagtccctt gaaggcaggg 4624 aaatagactt ctagaaaacc tgagaggaaa aagaattctt tttacaggag gcagcagaaa 4684 actgtctgaa aggtcaattg ttttatctcc ctttccactc tctttccaat ttcactttgg 4744 tggtctgaag aagaaaaaga aattttatgt atgtatgtgt aaatatgtgt atatatttct 4804 atctcttgct acaataattc caactaagtg aacttcttct caattatcat catacttact 4864 taccttatat taacaaatta agatgatgct gccaaaacaa gtctagcagg gaaaacaggt 4924 tctacatttt tcttaaataa attagggagt aaaagttata cttaacttgt ctgtctatta 4984 ttttaaaata tgcattgaaa taatgtggta taacttctct ggagtgcaat tttaagtcta 5044 attcatgcag atgattgatt gtgattattg taagaaattt cntacatgta tatttcttat 5104 gttagaaaat actgtttcta ctcattcaaa gcacattgta gatattcaga gagaagaaca 5164 aatggctggc ttggcaaatc cccatctgag ataaagtaaa caagtgacca gcagcccaca 5224 gataattcct ttatatagat gtataatgat tcaaactgct gcctttgcct ccagtgcatc 5284 cttacttagg tattatactt ctttaaaaag ctctgaagct gctacaatag aaaaatcaaa 5344 aagggtaaca gtatctgaaa tttcacagtc ctatccgatc tgaaaacaca catacacaaa 5404 tgcacacaca tgcacacaca catttcaggg acatagcagt aacactgttt tttaacaaca 5464 acaaaagttt aggttctaat ttatgtaaat acctagtatg tgtatttttg actttacaaa 5524 gtctttcttt tctgaaatct tcgtggtatg gcttttttaa ttcttttgac agcttatcag 5584 tctgtaggag aatgatcttg aaatgttnac cctgactaaa atttgggagc atatgccttg 5644 ctatattatc aagctggtca aggtagaaat actgatatgt atcatcacct tttccagata 5704 caaacttgcc ttattttcta gttngtgaac aagaacgaat gaagtactat tattgataac 5764 ttacttatat atttttattt agagcaatcc cacatgcttt tcacaaacat taaaaaaaaa 5824 aa 5826 62 522 DNA Homo sapiens CDS (133)..(510) 62 acggcgagtg aattgaattt aggtgacact atagaagagc tatgacgtcg catgcacgcg 60 tacgtaagct tggatcctct agagcggccg cctactacta ctactaaatt cgcggccgcg 120 tcgaccgcag cc atg gct cgt ggt ccc aag aag cat ctg aag cgg gtg 168 Met Ala Arg Gly Pro Lys Lys His Leu Lys Arg Val 1 5 10 gca gct cca aag cat tgg atg ctg gat aaa ttg acc ggt gtg ttt gct 216 Ala Ala Pro Lys His Trp Met Leu Asp Lys Leu Thr Gly Val Phe Ala 15 20 25 cct cgt cca tcc acc ggt ccc cac aag ttg aga gag tgt ctc ccc ctc 264 Pro Arg Pro Ser Thr Gly Pro His Lys Leu Arg Glu Cys Leu Pro Leu 30 35 40 atc att ttc ctg agg aac aga ctt aag tat gcc ctg aca gga gat gaa 312 Ile Ile Phe Leu Arg Asn Arg Leu Lys Tyr Ala Leu Thr Gly Asp Glu 45 50 55 60 gta aag aag att tgc atg cag cgg ttc att aaa atc gat ggc aag gtc 360 Val Lys Lys Ile Cys Met Gln Arg Phe Ile Lys Ile Asp Gly Lys Val 65 70 75 cga act gat ata acc tac cct gct gga ttc atg gat gtc atc agc att 408 Arg Thr Asp Ile Thr Tyr Pro Ala Gly Phe Met Asp Val Ile Ser Ile 80 85 90 gac aag acg gga gag aat ttc cgt ctg atc tat gac acc aag ggt cgc 456 Asp Lys Thr Gly Glu Asn Phe Arg Leu Ile Tyr Asp Thr Lys Gly Arg 95 100 105 ttt gct gta cat cgt att aca cct gag gag gcc aag tac aat ttg tgc 504 Phe Ala Val His Arg Ile Thr Pro Glu Glu Ala Lys Tyr Asn Leu Cys 110 115 120 aag tga gaagattttt tt 522 Lys * 125 63 522 DNA Homo sapiens CDS (54)..(467) 63 atttggccct cgaggccaag aattcggcac gagggaagag ggaaggctta gcc atg 56 Met 1 tcg tcc ttg atc aga agg gtg atc agc acc gcg aaa gcc cca ggg gcc 104 Ser Ser Leu Ile Arg Arg Val Ile Ser Thr Ala Lys Ala Pro Gly Ala 5 10 15 att gga ccc tac agt caa gct gta tta gtc gac agg acc att tac att 152 Ile Gly Pro Tyr Ser Gln Ala Val Leu Val Asp Arg Thr Ile Tyr Ile 20 25 30 tca gga cag ata ggc atg gac cct tca agt gga cag ctt gtg tca gga 200 Ser Gly Gln Ile Gly Met Asp Pro Ser Ser Gly Gln Leu Val Ser Gly 35 40 45 ggg gta gca gaa gaa gct aaa caa gct ctt aaa aac atg ggt gaa att 248 Gly Val Ala Glu Glu Ala Lys Gln Ala Leu Lys Asn Met Gly Glu Ile 50 55 60 65 ctg aaa gct gca ggc tgt gac ttc act aac gtg gtg aaa aca act gtt 296 Leu Lys Ala Ala Gly Cys Asp Phe Thr Asn Val Val Lys Thr Thr Val 70 75 80 ctt ctg gct gac ata aat gac ttc aat act gtc aat gaa atc tac aaa 344 Leu Leu Ala Asp Ile Asn Asp Phe Asn Thr Val Asn Glu Ile Tyr Lys 85 90 95 cag tat ttc aag agt aat ttt cct gct aga gct gct tac caa gtt gct 392 Gln Tyr Phe Lys Ser Asn Phe Pro Ala Arg Ala Ala Tyr Gln Val Ala 100 105 110 gct tta ccc aaa ggc agc cga att gaa att gaa gca gta gct atc caa 440 Ala Leu Pro Lys Gly Ser Arg Ile Glu Ile Glu Ala Val Ala Ile Gln 115 120 125 gga cca ctg aca acg gca tca cta taa gtggg cccagtgctg tgtagtctgg 492 Gly Pro Leu Thr Thr Ala Ser Leu * 130 135 aattgttaac attttaattt ttacaattga 522 64 1317 DNA Homo sapiens CDS (82)..(1161) 64 ccactttgta caagaaagct gggtacgcgt aagcttgggc ccctcgaggg atactctaga 60 gcggccgctg gagcccgagc c atg cgg acc gcg gac cgg gag gcg cgc ccg 111 Met Arg Thr Ala Asp Arg Glu Ala Arg Pro 1 5 10 ggg ctt ccg tcc ctg ctg ctg ctg ctg ctg gcc ggg gcc ggg ctg tca 159 Gly Leu Pro Ser Leu Leu Leu Leu Leu Leu Ala Gly Ala Gly Leu Ser 15 20 25 gcc gcc tcg ccc cca gca gcg ccg cgc ttc aac gtg agc ctg gac tcg 207 Ala Ala Ser Pro Pro Ala Ala Pro Arg Phe Asn Val Ser Leu Asp Ser 30 35 40 gtc ccc gag ctg cgc tgg ctg ccc gtg ctg cgg cac tac gac ttg gac 255 Val Pro Glu Leu Arg Trp Leu Pro Val Leu Arg His Tyr Asp Leu Asp 45 50 55 ttg gtg cgc gcc gcg atg gcg caa gtc atc ggg gac aga gtc ccc aag 303 Leu Val Arg Ala Ala Met Ala Gln Val Ile Gly Asp Arg Val Pro Lys 60 65 70 tgg gtg cac gtg tta atc gga aaa gtg gtc ctg gag ctg gag cgc ttc 351 Trp Val His Val Leu Ile Gly Lys Val Val Leu Glu Leu Glu Arg Phe 75 80 85 90 ctg ccc cag ccc ttc acc ggc gag atc cgc ggc atg tgt gac ttc atg 399 Leu Pro Gln Pro Phe Thr Gly Glu Ile Arg Gly Met Cys Asp Phe Met 95 100 105 aac ctc agc ctg gcg gac tgc ctt ctg gtc aac ctg gcc tac gag tcc 447 Asn Leu Ser Leu Ala Asp Cys Leu Leu Val Asn Leu Ala Tyr Glu Ser 110 115 120 tcc gtg ttc tgc acc agt att gtg gct caa gac tcc aga ggc cac att 495 Ser Val Phe Cys Thr Ser Ile Val Ala Gln Asp Ser Arg Gly His Ile 125 130 135 tac cat ggt cgg aat ttg gat tat cct ttt ggg aat gtc tta cgc aag 543 Tyr His Gly Arg Asn Leu Asp Tyr Pro Phe Gly Asn Val Leu Arg Lys 140 145 150 ctg aca gtg gat gtg caa ttc tta aag aat ggg cag att gca ttc aca 591 Leu Thr Val Asp Val Gln Phe Leu Lys Asn Gly Gln Ile Ala Phe Thr 155 160 165 170 gga act act ttt att ggc tat gta gga tta tgg act ggc cag agc cca 639 Gly Thr Thr Phe Ile Gly Tyr Val Gly Leu Trp Thr Gly Gln Ser Pro 175 180 185 cac aag ttt aca gtt tct ggt gat gaa cga gat aaa ggc tgg tgg tgg 687 His Lys Phe Thr Val Ser Gly Asp Glu Arg Asp Lys Gly Trp Trp Trp 190 195 200 gag aat gct atc gct gcc ctg ttt cgg aga cac att ccc gtc agc tgg 735 Glu Asn Ala Ile Ala Ala Leu Phe Arg Arg His Ile Pro Val Ser Trp 205 210 215 ctg atc cgc gct acc ctg agt gag tcg gaa aac ttc gaa gca gct gtt 783 Leu Ile Arg Ala Thr Leu Ser Glu Ser Glu Asn Phe Glu Ala Ala Val 220 225 230 ggc aag ttg gcc aag act ccc ctt att gct gat gtt tat tac att gtt 831 Gly Lys Leu Ala Lys Thr Pro Leu Ile Ala Asp Val Tyr Tyr Ile Val 235 240 245 250 ggt ggc acg tcc ccc cgg gag ggg gtg gtc atc acg agg aac aga gat 879 Gly Gly Thr Ser Pro Arg Glu Gly Val Val Ile Thr Arg Asn Arg Asp 255 260 265 ggc cca gca gac att tgg cct cta gat cct ttg aat gga gcg tgg ttc 927 Gly Pro Ala Asp Ile Trp Pro Leu Asp Pro Leu Asn Gly Ala Trp Phe 270 275 280 cga gtt gag aca aat tac gac cac tgg aag cca gca ccc aag gaa gat 975 Arg Val Glu Thr Asn Tyr Asp His Trp Lys Pro Ala Pro Lys Glu Asp 285 290 295 gac cgg aga aca tct gcc atc aag gcc ctt aat gct aca gga caa gca 1023 Asp Arg Arg Thr Ser Ala Ile Lys Ala Leu Asn Ala Thr Gly Gln Ala 300 305 310 aac ctc agc ctg gag gca ctt ttc cag att ttg tcg gtg gtt cca gtt 1071 Asn Leu Ser Leu Glu Ala Leu Phe Gln Ile Leu Ser Val Val Pro Val 315 320 325 330 tat aac aac ctc aca att tat act acg gta atg agc gcc ggt agc cca 1119 Tyr Asn Asn Leu Thr Ile Tyr Thr Thr Val Met Ser Ala Gly Ser Pro 335 340 345 gac aag tac atg act agg atc aga aac ccg agt aga aag taa gtcagca 1168 Asp Lys Tyr Met Thr Arg Ile Arg Asn Pro Ser Arg Lys * 350 355 360 gaagagcgag ttcgcccgtg ctgtgaaaga tgatttttta aaaaatgaaa ttcttgaaga 1228 gctgcacctt aaaaaataag acaaagtgaa agtattggat tatgttacac acaatgcagg 1288 ctccttcctc attgaacttt acaaccttg 1317 65 1205 DNA Homo sapiens CDS (136)..(792) 65 atttggccct cgaggccaag aattcggcac gagggaagcc cagtacattt caagttggtc 60 gcggcttggg ctccgctttg gggaggggca gcaggtttat tcactggatc tctgaatacc 120 caggccccct ccacc atg gcc agc cgg ggt ggg ggc cgg ggt cgt ggc cgg 171 Met Ala Ser Arg Gly Gly Gly Arg Gly Arg Gly Arg 1 5 10 ggc cag ttg acc ttc aac gtg gag gcc gtg ggc att ggg aaa ggg gat 219 Gly Gln Leu Thr Phe Asn Val Glu Ala Val Gly Ile Gly Lys Gly Asp 15 20 25 gct ttg ccc cca ccc acc ctg cag cct tct cca ctc ttc cct ccc ttg 267 Ala Leu Pro Pro Pro Thr Leu Gln Pro Ser Pro Leu Phe Pro Pro Leu 30 35 40 gag ttc cgc cca gta cct ttg ccc tca ggc gag gaa ggg gaa tat gtc 315 Glu Phe Arg Pro Val Pro Leu Pro Ser Gly Glu Glu Gly Glu Tyr Val 45 50 55 60 ctg gca ctg aag caa gag cta cga gga gcc atg agg cag ctc ccc tac 363 Leu Ala Leu Lys Gln Glu Leu Arg Gly Ala Met Arg Gln Leu Pro Tyr 65 70 75 ttc atc cgg cca gct gtc ccc aag aga gat gtg gag cgt tat tca gac 411 Phe Ile Arg Pro Ala Val Pro Lys Arg Asp Val Glu Arg Tyr Ser Asp 80 85 90 aaa tat cag atg tca ggt ccg att gac aat gcc atc gat tgg aac cct 459 Lys Tyr Gln Met Ser Gly Pro Ile Asp Asn Ala Ile Asp Trp Asn Pro 95 100 105 gat tgg cgg cgt cta ccc cgg gag cta aag atc cga gtg cgg aag cta 507 Asp Trp Arg Arg Leu Pro Arg Glu Leu Lys Ile Arg Val Arg Lys Leu 110 115 120 cag aag gaa cgg att aca att ctg ctc ccc aag agg ccc cct aag acc 555 Gln Lys Glu Arg Ile Thr Ile Leu Leu Pro Lys Arg Pro Pro Lys Thr 125 130 135 140 aca gaa gat aag gag gaa aca ata cag aaa cta gag acc ctg gag aag 603 Thr Glu Asp Lys Glu Glu Thr Ile Gln Lys Leu Glu Thr Leu Glu Lys 145 150 155 aag gaa gaa gaa gta act tca gag gag gat gag gag aaa gaa gaa gaa 651 Lys Glu Glu Glu Val Thr Ser Glu Glu Asp Glu Glu Lys Glu Glu Glu 160 165 170 gaa gag aag gaa gag gag gaa gaa gaa gag tat gat gaa gaa gaa cat 699 Glu Glu Lys Glu Glu Glu Glu Glu Glu Glu Tyr Asp Glu Glu Glu His 175 180 185 gaa gag gaa act gat tac atc atg tca tat ttt gac aat gga gag gac 747 Glu Glu Glu Thr Asp Tyr Ile Met Ser Tyr Phe Asp Asn Gly Glu Asp 190 195 200 ttt ggt ggt gac agt gat gac aat atg gac gag gct ata tac tga aga 795 Phe Gly Gly Asp Ser Asp Asp Asn Met Asp Glu Ala Ile Tyr * 205 210 215 aggactctgg accctcgtgt ctttctttag gatacagaga gtaactgtac ctattatttg 855 tttcttcaga caagcaaatc atttggtcag agttcatata atctgtctgt tccctggaga 915 tgggaataga ggatgatgac agtttatttt ctacacttcc cctccttcca catttgtatc 975 acctttgcta tcttggggaa agtgcaaagg acaaacatct caattgtatg aagggagaaa 1035 ggagaattga aagaagaact ggggttgtta gagctgagat gactgtacac atacccctgc 1095 ccaatttata tagctctttg tggagataat taggggtggg agcagtttga aggagtaagc 1155 ctggttttat acttttaaat aaagtgtttt tatctgtcaa aaaaaaaaaa 1205 66 448 DNA Homo sapiens CDS (106)..(291) 66 gactcactat agggaatttg gccctcgagg ccaagaattc ggcacgagct gtcccgctgc 60 gtgttttcct cttgatcggg aactcctgct tctccttgcc tcgaa atg gac ccc 114 Met Asp Pro 1 aac tgc tcc tgc tcg cct gtt ggc tcc tgt gcc tgt gcc ggc tcc tgc 162 Asn Cys Ser Cys Ser Pro Val Gly Ser Cys Ala Cys Ala Gly Ser Cys 5 10 15 aaa tgc aaa gag tgc aaa tgc acc tcc tgc aag aag agc tgc tgc tcc 210 Lys Cys Lys Glu Cys Lys Cys Thr Ser Cys Lys Lys Ser Cys Cys Ser 20 25 30 35 tgc tgc cct gtg ggc tgt gcc aag tgt gcc cag ggc tgc atc tgc aaa 258 Cys Cys Pro Val Gly Cys Ala Lys Cys Ala Gln Gly Cys Ile Cys Lys 40 45 50 ggg acg tca gac aag tgc agc tgc tgt gcc tga tgccagga cagctgtgct 309 Gly Thr Ser Asp Lys Cys Ser Cys Cys Ala * 55 60 ctcagatgta aatagagcaa cctatataaa cctggatttt tttttttttt tttttgtaca 369 accctgaccc gtttgctaca tctttttttc tatgaaatat gtgaatggca ataaattcat 429 ctagactaaa aaaaaaaaa 448 67 2410 DNA Homo sapiens CDS (121)..(1116) 67 gtcccctcag agggttcctg ctgctgccgg tgccttggac cctccccctc gcttctcgtt 60 ctactgcccc aggagcccgg cgggtccggg actcccgtcc gtgccggtgc gggcgccggc 120 atg tgg ctg tgg gag gac cag ggc ggc ctc ctg ggc cct ttc tcc ttc 168 Met Trp Leu Trp Glu Asp Gln Gly Gly Leu Leu Gly Pro Phe Ser Phe 1 5 10 15 ctg ctg cta gtg ctg ctg ctg gtg acg cgg agc ccg gtc aat gcc tgc 216 Leu Leu Leu Val Leu Leu Leu Val Thr Arg Ser Pro Val Asn Ala Cys 20 25 30 ctc ctc acc ggc agc ctc ttc gtt cta ctg cgc gtc ttc agc ttt gag 264 Leu Leu Thr Gly Ser Leu Phe Val Leu Leu Arg Val Phe Ser Phe Glu 35 40 45 ccg gtg ccc tct tgc agg gcc ctg cag gtg ctc aag ccc cgg gac cgc 312 Pro Val Pro Ser Cys Arg Ala Leu Gln Val Leu Lys Pro Arg Asp Arg 50 55 60 att tct gcc atc gcc cac cgt ggc ggc agc cac gac gcg ccc gag aac 360 Ile Ser Ala Ile Ala His Arg Gly Gly Ser His Asp Ala Pro Glu Asn 65 70 75 80 acg ctg gcg gcc att cgg cag gca gct aag aat gga gca aca ggc gtg 408 Thr Leu Ala Ala Ile Arg Gln Ala Ala Lys Asn Gly Ala Thr Gly Val 85 90 95 gag ttg gac att gag ttt act tct gac ggg att cct gtc tta atg cac 456 Glu Leu Asp Ile Glu Phe Thr Ser Asp Gly Ile Pro Val Leu Met His 100 105 110 gat aac aca gta gat agg acg act gat ggg act ggg cga ttg tgt gat 504 Asp Asn Thr Val Asp Arg Thr Thr Asp Gly Thr Gly Arg Leu Cys Asp 115 120 125 ttg aca ttt gaa caa att agg aag ctg aat cct gca gca aac cac aga 552 Leu Thr Phe Glu Gln Ile Arg Lys Leu Asn Pro Ala Ala Asn His Arg 130 135 140 ctc agg aat gat ttc cct gat gaa aag atc cct acc cta agg gaa gct 600 Leu Arg Asn Asp Phe Pro Asp Glu Lys Ile Pro Thr Leu Arg Glu Ala 145 150 155 160 gtt gca gag tgc cta aac cat aac ctc aca atc ttc ttt gat gtc aaa 648 Val Ala Glu Cys Leu Asn His Asn Leu Thr Ile Phe Phe Asp Val Lys 165 170 175 ggc cat gca cac aag gct act gag gct cta aag aaa atg tat atg gaa 696 Gly His Ala His Lys Ala Thr Glu Ala Leu Lys Lys Met Tyr Met Glu 180 185 190 ttt cct caa ctg tat aat aat agt gtg gtc tgt tct ttc ttg cca gaa 744 Phe Pro Gln Leu Tyr Asn Asn Ser Val Val Cys Ser Phe Leu Pro Glu 195 200 205 gtt atc tac aag atg aga caa aca gat cgg gat gta ata aca gca tta 792 Val Ile Tyr Lys Met Arg Gln Thr Asp Arg Asp Val Ile Thr Ala Leu 210 215 220 act cac aga cct tgg agc cta agc cat aca gga gat ggg aaa cca cgc 840 Thr His Arg Pro Trp Ser Leu Ser His Thr Gly Asp Gly Lys Pro Arg 225 230 235 240 tat gat act ttc tgg aaa cat ttt ata ttt gtt atg atg gac att ttg 888 Tyr Asp Thr Phe Trp Lys His Phe Ile Phe Val Met Met Asp Ile Leu 245 250 255 ctc gat tgg agc atg cat aat atc ttg tgg tac ctg tgt gga att tca 936 Leu Asp Trp Ser Met His Asn Ile Leu Trp Tyr Leu Cys Gly Ile Ser 260 265 270 gct ttc ctc atg caa aag gat ttt gta tcc ccg gcc tac ttg aag aag 984 Ala Phe Leu Met Gln Lys Asp Phe Val Ser Pro Ala Tyr Leu Lys Lys 275 280 285 tgg tca gct aaa gga atc cag gtt gtt ggt tgg act gtt aat acc ttt 1032 Trp Ser Ala Lys Gly Ile Gln Val Val Gly Trp Thr Val Asn Thr Phe 290 295 300 gat gaa aag agt tac tac gaa tcc cat ctt ggt tcc agc tat atc act 1080 Asp Glu Lys Ser Tyr Tyr Glu Ser His Leu Gly Ser Ser Tyr Ile Thr 305 310 315 320 gac agc atg gta gaa gac tgc gaa cct cac ttc tag actt tcacggtggg 1130 Asp Ser Met Val Glu Asp Cys Glu Pro His Phe * 325 330 acgaaacggg ttcagaaact gccaggggcc tcatacaggg atatcaaaat accctttgtg 1190 ctagcccagg ccctggggaa tcaggtgact cacacaaatg caatagttgg tcactgcatt 1250 tttacctgaa ccaaagctaa acccggtgtt gccaccatgc accatggcat gccagagttc 1310 aacactgttg ctcttgaaaa tctgggtctg aaaaaacgca caagagcccc tgccctgccc 1370 tagctgaggc acacagggag acccagtgag gataagcaca gattgaattg tacagtttgc 1430 agatgcagat gtaaatgcat gggacatgca tgataactca gagttgacat tttaaaactt 1490 gccacactta tttcaaatat ttgtactcag ctatgttaac atgtactgta gacatcaaac 1550 ttgtggccat actaataaaa ttattaaaag gagcactaaa ggaaaactgt gtgccaagca 1610 tcatagccta agccatacag gagatgggaa accacgctat gatactttct ggaaacattt 1670 tatatttgtt atgatggaca ttttgctcga ttggagcatg cataatatct tgtggtacct 1730 gtgtggaatt tcagctttcc tcatgcaaaa ggattttgta tccccggcct acttgaagaa 1790 gtggtcagct aaaggaatcc aggttgttgg ttggactgtt aatacctttg atgaaaagag 1850 ttactacgaa tcccatcttg gttccagcta tatcactgac agcatggtag aagactgcga 1910 acctcacttc tagactttca cggtgggacg aaacgggttc agaaactgcc aggggcctca 1970 tacagggata tcaaaatacc ctttgtgcta gcccaggccc tggggaatca ggtgactcac 2030 acaaatgcaa tagttggtca ctgcattttt acctgaacca aagctaaacc cggtgttgcc 2090 accatgcacc atggcatgcc agagttcaac actgttgctc ttgaaaatct gggtctgaaa 2150 aaacgcacaa gagcccctgc cctgccctag ctgaggcaca cagggagacc cagtgaggat 2210 aagcacagat tgaattgtac agtttgcaga tgcagatgta aatgcatggg acatgcatga 2270 taactcagag ttgacatttt aaaacttgcc acacttattt caaatatttg tactcagcta 2330 tgttaacatg tactgtagac atcaaacttg tggccatact aataaaatta ttaaaaggag 2390 cactaaagga aaaaaaaaaa 2410 68 1464 DNA Homo sapiens CDS (373)..(1464) 68 atggcccccg ctccgccccc cgccgcctcc ttctcgccct ccgaggtcca gcggcgcctg 60 gcggccggcg cgtgctgggt ccgccgcggg gcccgcctct acgacctctc cagcttcgtg 120 cggcaccacc cggggggcga gcagctgctg cgggccaggg cgggccagga catcagcgcc 180 gacctggacg ggccgccgca caggcactcg gccaacgcgc gccgctggct ggagcagtac 240 tacgtgggag agctccgcgg ggagcagcag acaggtgata agcatcccat gcgctctgaa 300 acccaccaca tcacagaaac agcccttgct ggcgttacca ggaccttcgc cttcctccac 360 ccggtgggct cc atg gag aac gag cct gta gcc ctt gag gaa act cag 408 Met Glu Asn Glu Pro Val Ala Leu Glu Glu Thr Gln 1 5 10 aag aca gat cct gct atg gaa cca cgg ttc aaa gtg gtg gat tgg gac 456 Lys Thr Asp Pro Ala Met Glu Pro Arg Phe Lys Val Val Asp Trp Asp 15 20 25 aag aac aca gcc agt ggc tgc ctg act ccc cgt gct gaa gat tgg ctg 504 Lys Asn Thr Ala Ser Gly Cys Leu Thr Pro Arg Ala Glu Asp Trp Leu 30 35 40 agc atc cac cga gac acc ctc atc ctc act ccg att gtg tgt ggc aga 552 Ser Ile His Arg Asp Thr Leu Ile Leu Thr Pro Ile Val Cys Gly Arg 45 50 55 60 ttg ggg ccc acc agc atc aca gat gag ggc act gag ggg ctc cgg gag 600 Leu Gly Pro Thr Ser Ile Thr Asp Glu Gly Thr Glu Gly Leu Arg Glu 65 70 75 gaa aag atg cac gtc cag gat ctc aca gct ggt caa agg cac agc cag 648 Glu Lys Met His Val Gln Asp Leu Thr Ala Gly Gln Arg His Ser Gln 80 85 90 gct cta atg gac ctg gtg gac tgg cga aag cct ctc ctg tgg cag gtg 696 Ala Leu Met Asp Leu Val Asp Trp Arg Lys Pro Leu Leu Trp Gln Val 95 100 105 ggc cac ttg gga gag aag tac gat gag tgg gtt cac cag ccg gtg acc 744 Gly His Leu Gly Glu Lys Tyr Asp Glu Trp Val His Gln Pro Val Thr 110 115 120 agg ccc atc cgc ctc ttc cac tca gac ctc att gag ggc ctc tct aag 792 Arg Pro Ile Arg Leu Phe His Ser Asp Leu Ile Glu Gly Leu Ser Lys 125 130 135 140 act gtc tgg tac agt gtc ccc atc atc tgg gtg ccc ctg gtg ctg tat 840 Thr Val Trp Tyr Ser Val Pro Ile Ile Trp Val Pro Leu Val Leu Tyr 145 150 155 ctc agc tgg tcc tac tac cga acc ttt gcc cag ggc aac gtc cga ctc 888 Leu Ser Trp Ser Tyr Tyr Arg Thr Phe Ala Gln Gly Asn Val Arg Leu 160 165 170 ttc acg tca ttt aca aca gag tac acg gtg gca gtg ccc aag tcc atg 936 Phe Thr Ser Phe Thr Thr Glu Tyr Thr Val Ala Val Pro Lys Ser Met 175 180 185 ttc ccc ggg ctc ttc atg ctg ggg aca ttc ctc tgg agc ctc atc gag 984 Phe Pro Gly Leu Phe Met Leu Gly Thr Phe Leu Trp Ser Leu Ile Glu 190 195 200 tac ctc atc cac cgc ttc ctg ttc cac atg aag ccc ccc agc gac agc 1032 Tyr Leu Ile His Arg Phe Leu Phe His Met Lys Pro Pro Ser Asp Ser 205 210 215 220 tat tac ctc atc atg ctg cac ttc gtc atg cac ggc cag cac cac aag 1080 Tyr Tyr Leu Ile Met Leu His Phe Val Met His Gly Gln His His Lys 225 230 235 gca ccc ttc gac ggc tcc cgc ctg gtc ttc ccc cct gtg cca gcc tcc 1128 Ala Pro Phe Asp Gly Ser Arg Leu Val Phe Pro Pro Val Pro Ala Ser 240 245 250 ctg gtg atc ggc gtc ttc tac ttg tgc atg cag ctc atc ctg ccc gag 1176 Leu Val Ile Gly Val Phe Tyr Leu Cys Met Gln Leu Ile Leu Pro Glu 255 260 265 gca gta ggg ggc act gtg ttt gcg ggg ggc ctc ctg ggc tac gtc ctc 1224 Ala Val Gly Gly Thr Val Phe Ala Gly Gly Leu Leu Gly Tyr Val Leu 270 275 280 tat gac atg acc cat tac tac ctg cac ttt ggc tcg ccg cac aag ggc 1272 Tyr Asp Met Thr His Tyr Tyr Leu His Phe Gly Ser Pro His Lys Gly 285 290 295 300 tcc tac ctg tac agc ctg aag gcc cac cac gtc aag cac cac ttt gca 1320 Ser Tyr Leu Tyr Ser Leu Lys Ala His His Val Lys His His Phe Ala 305 310 315 cat cag aag tca gga ggg tca cat cca ctt ggt ggc cag gtg gcc ctt 1368 His Gln Lys Ser Gly Gly Ser His Pro Leu Gly Gly Gln Val Ala Leu 320 325 330 ggt gac cca ctt ctt cct gga gcg tcc ctg cct aga gct cag ccc aca 1416 Gly Asp Pro Leu Leu Pro Gly Ala Ser Leu Pro Arg Ala Gln Pro Thr 335 340 345 gga ctg ctt cag gcc gtg gcc aca ggt agc agc cgc aag ggg aaa tga 1464 Gly Leu Leu Gln Ala Val Ala Thr Gly Ser Ser Arg Lys Gly Lys * 350 355 360 69 926 DNA Homo sapiens CDS (80)..(661) 69 ggtaccggtc cggaattccc gggtcgacga tttcgtggct ccgagccgag cgcgcggagc 60 agctggggcc ggggcgcgg atg ctg gaa gtt cac atc ccg tcg gtg ggg ccc 112 Met Leu Glu Val His Ile Pro Ser Val Gly Pro 1 5 10 gag gcc gag ggg ccc agg cag agc ccg gag aaa agc cac atg gtg ttc 160 Glu Ala Glu Gly Pro Arg Gln Ser Pro Glu Lys Ser His Met Val Phe 15 20 25 cga gtg gag gtg ctg tgc agc ggg cgc aga cac acg gtg cca agg cgc 208 Arg Val Glu Val Leu Cys Ser Gly Arg Arg His Thr Val Pro Arg Arg 30 35 40 tac agc gag ttc cac gcg ctg cac aag cgg atc aag aag ctg tac aaa 256 Tyr Ser Glu Phe His Ala Leu His Lys Arg Ile Lys Lys Leu Tyr Lys 45 50 55 gtg ccc gac ttc ccc tcg aaa cgc ctg ccc aac tgg agg acc aga ggg 304 Val Pro Asp Phe Pro Ser Lys Arg Leu Pro Asn Trp Arg Thr Arg Gly 60 65 70 75 ttg gaa cag cgc cgg cag ggc ttg gag gct tac atc cag ggc atc ctg 352 Leu Glu Gln Arg Arg Gln Gly Leu Glu Ala Tyr Ile Gln Gly Ile Leu 80 85 90 tac ctg aac cag gag gtg ccc aag gag tta ctg gaa ttc ctg aga ctt 400 Tyr Leu Asn Gln Glu Val Pro Lys Glu Leu Leu Glu Phe Leu Arg Leu 95 100 105 cgg cac ttc ccc aca gac ccc aag gct agc aac tgg ggc acc ctg agg 448 Arg His Phe Pro Thr Asp Pro Lys Ala Ser Asn Trp Gly Thr Leu Arg 110 115 120 gag ttc ctg cct ggc gac agc agc tcc cag cag cac cag cgg cct gtc 496 Glu Phe Leu Pro Gly Asp Ser Ser Ser Gln Gln His Gln Arg Pro Val 125 130 135 ctg agc ttc cat gtg gat ccc tat gtt tgc aac ccc tcc cca gag tcg 544 Leu Ser Phe His Val Asp Pro Tyr Val Cys Asn Pro Ser Pro Glu Ser 140 145 150 155 ctg ccc aac gtg gtg gtg aat ggt gtg ctc cag ggc ctc tac agc ttc 592 Leu Pro Asn Val Val Val Asn Gly Val Leu Gln Gly Leu Tyr Ser Phe 160 165 170 agc atc agc cca gat aaa gcc cag cca aag gcg gcc tgt cac cct gct 640 Ser Ile Ser Pro Asp Lys Ala Gln Pro Lys Ala Ala Cys His Pro Ala 175 180 185 cct ctg cca ccg atg ccc tga tc agtccagagg cctttggctg cctcctaaga 693 Pro Leu Pro Pro Met Pro * 190 aagtcatgtg cctctgtcct atgaactcca tataaggctg ggtcctcctt tggcctggac 753 ccaggactta attacccagt gcccagttgt gccacattcc cactcaaggc tcagaacttg 813 gctcgcattg gtagctggag gtggtagaat ttgtatgctc ttagagccca acagccaagg 873 cagggtcaag aagataagta ataaaagagg aagtcagcca aaaaaaaaaa aaa 926 70 4221 DNA Homo sapiens CDS (269)..(1603) 70 cgaccgctcc ggaattcccg ggtcgacgat ttcgtccgga agtgcggatc ccagcggcgg 60 ccgtgtagct gagcagccct ggggcttggt tctatgtccc tgtggctatg tttccagtgt 120 cctctgggtg tttccaagag caacaagaaa cgaataaatc tctggcaaag gcagctcgag 180 catctcatct gacgtgagtt caagtacaga tcacacgccc actaaagccc agaagaatgt 240 ggctaccagc gaagactccg acctgagc atg cgc aca ctg agc acg ccc agc 292 Met Arg Thr Leu Ser Thr Pro Ser 1 5 ccg gcc ctg ata tgt cca ccg aat ctc cca gga ttt cag aat gga agg 340 Pro Ala Leu Ile Cys Pro Pro Asn Leu Pro Gly Phe Gln Asn Gly Arg 10 15 20 ggc tcg tcc acc tcc tcg tcc tcc atc acc ggg gag acg gtg gcc atg 388 Gly Ser Ser Thr Ser Ser Ser Ser Ile Thr Gly Glu Thr Val Ala Met 25 30 35 40 gtg cac tcc ccg ccc ccg acc cgc ctc aca cac ccg ctc atc cgg ctc 436 Val His Ser Pro Pro Pro Thr Arg Leu Thr His Pro Leu Ile Arg Leu 45 50 55 gcc tcc aga ccc cag aag gag cag gcc agc ata gac cgg ctc ccg gac 484 Ala Ser Arg Pro Gln Lys Glu Gln Ala Ser Ile Asp Arg Leu Pro Asp 60 65 70 cac tcc atg gtg cag atc ttc tcc ttc ctg ccc acc aac cag ctg tgc 532 His Ser Met Val Gln Ile Phe Ser Phe Leu Pro Thr Asn Gln Leu Cys 75 80 85 cgc tgc gcg cga gtg tgc cgc cgc tgg tac aac ctg gcc tgg gac ccg 580 Arg Cys Ala Arg Val Cys Arg Arg Trp Tyr Asn Leu Ala Trp Asp Pro 90 95 100 cgg ctc tgg agg act atc cgc ctg acg ggc gag acc atc aac gtg gac 628 Arg Leu Trp Arg Thr Ile Arg Leu Thr Gly Glu Thr Ile Asn Val Asp 105 110 115 120 cgc gcc ctc aag gtg ctg acc cgc aga ctc tgc cag gac acc ccc aac 676 Arg Ala Leu Lys Val Leu Thr Arg Arg Leu Cys Gln Asp Thr Pro Asn 125 130 135 gtg tgt ctc atg ctg gaa acc gta act gtc agt ggc tgc agg cgg ctc 724 Val Cys Leu Met Leu Glu Thr Val Thr Val Ser Gly Cys Arg Arg Leu 140 145 150 aca gac cga ggg ctg tac acc atc gcc cag tgc tgc ccc gaa ctg agg 772 Thr Asp Arg Gly Leu Tyr Thr Ile Ala Gln Cys Cys Pro Glu Leu Arg 155 160 165 cga ctg gaa gtc tca ggc tgt tac aat atc tcc aac gag gcc gtc ttt 820 Arg Leu Glu Val Ser Gly Cys Tyr Asn Ile Ser Asn Glu Ala Val Phe 170 175 180 gat gtg gtg tcc ctc tgc cct aat ctg gag cac ctg gat gtg tca gga 868 Asp Val Val Ser Leu Cys Pro Asn Leu Glu His Leu Asp Val Ser Gly 185 190 195 200 tgc tcc aaa gtg acc tgc atc agc ttg acc cgg gag gcc tcc att aaa 916 Cys Ser Lys Val Thr Cys Ile Ser Leu Thr Arg Glu Ala Ser Ile Lys 205 210 215 ctg tca ccc ttg cat ggc aaa cag att tcc atc cgc tac ctg gac atg 964 Leu Ser Pro Leu His Gly Lys Gln Ile Ser Ile Arg Tyr Leu Asp Met 220 225 230 acg gac tgc ttc gtg ctg gag gac gaa ggc ctg cac acc atc gcg gcg 1012 Thr Asp Cys Phe Val Leu Glu Asp Glu Gly Leu His Thr Ile Ala Ala 235 240 245 cac tgc acg cag ctc acc cac ctc tac ctg cgc cgc tgc gtc cgc ctg 1060 His Cys Thr Gln Leu Thr His Leu Tyr Leu Arg Arg Cys Val Arg Leu 250 255 260 acc gac gaa ggc ctg cgc tac ctg gtg atc tac tgc gcc tcc atc aag 1108 Thr Asp Glu Gly Leu Arg Tyr Leu Val Ile Tyr Cys Ala Ser Ile Lys 265 270 275 280 gag ctg agc gtc agc gac tgc cgc ttc gtc agc gac ttc ggc ctg cgg 1156 Glu Leu Ser Val Ser Asp Cys Arg Phe Val Ser Asp Phe Gly Leu Arg 285 290 295 gag atc gcc aag ctg gag tcc cgc ctg cgg tac ctg agc atc gcg cac 1204 Glu Ile Ala Lys Leu Glu Ser Arg Leu Arg Tyr Leu Ser Ile Ala His 300 305 310 tgc ggc cgg gtc acc gac gtg ggc atc cgc tac gtg gcc aag tac tgc 1252 Cys Gly Arg Val Thr Asp Val Gly Ile Arg Tyr Val Ala Lys Tyr Cys 315 320 325 agc aag ctg cgc tac ctc aac gcg agg ggc tgc gag ggc atc acg gac 1300 Ser Lys Leu Arg Tyr Leu Asn Ala Arg Gly Cys Glu Gly Ile Thr Asp 330 335 340 cac ggt gtg gag tac ctc gcc aag aac tgc acc aaa ctc aaa tcc ctg 1348 His Gly Val Glu Tyr Leu Ala Lys Asn Cys Thr Lys Leu Lys Ser Leu 345 350 355 360 gat atc ggc aaa tgc cct ttg gta tcc gac acg ggc ctg gag tgc ctg 1396 Asp Ile Gly Lys Cys Pro Leu Val Ser Asp Thr Gly Leu Glu Cys Leu 365 370 375 gcc ctg aac tgc ttc aac ctc aag cgg ctc agc ctc aag tcc tgc gag 1444 Ala Leu Asn Cys Phe Asn Leu Lys Arg Leu Ser Leu Lys Ser Cys Glu 380 385 390 agc atc acc ggc cag ggc ttg cag atc gtg gcc gcc aac tgc ttt gac 1492 Ser Ile Thr Gly Gln Gly Leu Gln Ile Val Ala Ala Asn Cys Phe Asp 395 400 405 ctc cag acg ctg aat gtc cag gac tgc gag gtc tcc gtg gag gcc ctg 1540 Leu Gln Thr Leu Asn Val Gln Asp Cys Glu Val Ser Val Glu Ala Leu 410 415 420 cgc ttt gtc aaa cgc cac tgc aag cgc tgc gtc atc gag cac acc aac 1588 Arg Phe Val Lys Arg His Cys Lys Arg Cys Val Ile Glu His Thr Asn 425 430 435 440 ccg gct ttc ttc tga agggacagag ttcatccggc gttgtattca cacaaacctg 1643 Pro Ala Phe Phe * 445 aacaaagcaa atttttttaa aagcagcgta tgtaagcacc gacacccact caaaacagct 1703 ctttcttccg ggaaggttat taggaatctg gcctttattt ttcctcattt ctcatgggca 1763 acagaggcca aagaaacgaa gcaagacaaa cagcaaacag gcattttggt caggtcattt 1823 gtaggcagtt tctcttctca caaaagatgt acttaagcag gctgatcgct gttccttgag 1883 caaggcgctt actctcctcc gctcaggccc ccaaggccgc cctttccctc gcacacaggc 1943 cccaccccca cagttccacg ccccccccac caaggccaca ccctccctcc ctagagcagc 2003 agcgaggatc catcatcaga atcacagtgc tctccagacc tcctctctaa actgcttcat 2063 tgacctaagt cactctcttc aatcccacac ccatggacat tcttgtcaac tcaataccat 2123 agcactttgc ataggcaaaa tacttttcag gcctttttaa aaaattcatt acagcaaaca 2183 gctggggaag gacatgcagt cctcccccag ctctgtcaat gactatgacc ttggccaaag 2243 cacttcactg ctctgggctg cagcttccag cactgaatca gaggccacac agcccaaaga 2303 ttagcttcat gtccattata gcattgaggg agcagagata cccatacaca gaagcacctt 2363 ggcatagagc acccaggcat cgacctcttc caggagaact gattctgtgg atggatgtga 2423 tttcaggaga ttgtgcagtg ccagcatcag tgcataaagg gtcctgtatg tcctttggct 2483 gcaaatcacc cacttccctg tgtttcagtg ggagaatttc ctctcccacc tcctcacatc 2543 ctcttttgcc aggctggatg ctgtcgtctc tgtacacaaa tactttctgc attcccccct 2603 ccacaccatc ctagcgaggc accagcacac ctaatcacag caaagcccag atccccccat 2663 cagttgcttt tactcagtgt tttcaaatag gagtaaaggc ccttgcaatt tttaattaac 2723 aagcaaggcc caagggaaca catgtcctca aaagtttttc tgatccctcg ccttgcacac 2783 ctggcatgca tcaggcacat ctgtcctaca gctggcagag acagatgcct cggttctttg 2843 tcattcagat tgcatttgac ctcttctcat ctatttattt ctttatacat ccagacttca 2903 tcacatgaag cctattgggg ttaagtttgt aagtgtttaa ttgtgcaaat tgccaccctg 2963 tgtacctcct ccatgtctgt ctgcgtgttt tccaccaaag aatgcaaagc agacttccag 3023 gtgtttaaat tctgttcact caacaatgcc agatgaatgg aagagggaac acactgagat 3083 gacttagact ctggtccacc aaccagaccc ttggaaagga atactaaaat cattacaagg 3143 tatggatttt aaatggatga aacttcaaat tatcttattt ggatagaagt ctatattcta 3203 gcctcatttg catgaagtca gatagccaga agaaattcca ttgctggttt tcacgaaatt 3263 cacttgtctt ttgctaataa acacatggcc ctttcccaga ttattctcta gccaagcccc 3323 acctttgtta cgttgaaatc cctcatttat tttcttctca aaatgcccat tatccaaatg 3383 cagaacctct gcatctccaa gccagttatg ctgaatttgt caaacttaga cacccttgac 3443 aactgcactc ctactgtagg ctcctgtgca tactgtcgtc ttctgtgggg gatggagagg 3503 ttagtgtgat gaggtggtgt ctgcccagga ggtttctttc aaacatcatg gcctcccatc 3563 caatcaacat catcaaatta catgtgtaat caaggctctg tgccatgggg gaaatgaatc 3623 atttagctag gccaggatct agtgaaagcc acagagttta aaaccatgaa agaagttgaa 3683 ggcagcattc ctcagctctg tgacttgtga ccctatttga agtttcagga tttgggtgtc 3743 acaaaggatt gtccctaatc cttggccctg gggtcttccg agtgagctgg tttaatactc 3803 tgagaatgag cagggagatc cagagaatga atccctgacc gcatcaccta aactgtcttc 3863 caaacatgag acaaagctga ctgttcacac tgattgccca gcacataccg tcttgccagt 3923 ttcttctttt ctcccagtct cctgttcatc cattctgttc tcccttgggg tgggaatcta 3983 tgatggaggt tactggggaa acagctcagc agatttttgg agaccaaacc aaaggtctca 4043 ctaggaaatt tatctgtttt aaaacattgc ttccttcctg gctctgctaa attgaatgct 4103 cattgtttgt tgttgttgtt ttttaattct aatgttcaaa tcactgcgtg ctgtatgaat 4163 ctagaaagcc ttaatttact accaagaaat aaagcaatat gttcgtaaaa aaaaaaaa 4221 71 519 DNA Homo sapiens CDS (132)..(431) 71 ggaattccta gggatgcaga tgggggaagg ggaagctgag aaagcagtga agacagaatg 60 agctggggaa gaggcagatg gacggggctg cagcatagga gtctcagctg cttacatcca 120 ggtccaggat t atg tct gct aac aga cgc tgg tgg gta cca cct gac gat 170 Met Ser Ala Asn Arg Arg Trp Trp Val Pro Pro Asp Asp 1 5 10 gaa gac tgt gtg tct gag aag ctc ctg agg aag act cgg gaa tct cca 218 Glu Asp Cys Val Ser Glu Lys Leu Leu Arg Lys Thr Arg Glu Ser Pro 15 20 25 ctg gtg cct ata ggc tta gga ggc tgc ttg gtg gta gca gca tac agg 266 Leu Val Pro Ile Gly Leu Gly Gly Cys Leu Val Val Ala Ala Tyr Arg 30 35 40 45 att tac cgg ctg agg tct cgt ggt tcc acc aag atg tcc ata cac ctg 314 Ile Tyr Arg Leu Arg Ser Arg Gly Ser Thr Lys Met Ser Ile His Leu 50 55 60 att cac acc cga gtg gca gcg cag gcc tgt gca gtg ggt gca atc atg 362 Ile His Thr Arg Val Ala Ala Gln Ala Cys Ala Val Gly Ala Ile Met 65 70 75 cta ggt gct gtg tac aca atg tac agc gat tac gtc aag agg atg gca 410 Leu Gly Ala Val Tyr Thr Met Tyr Ser Asp Tyr Val Lys Arg Met Ala 80 85 90 cag gat gct gga gag aag tag ga ctccaatagg agccggggct gtccaactcc 463 Gln Asp Ala Gly Glu Lys * 95 100 cctaactcaa tccctggtac attcctaata aagcagtttt gaggaaaaaa aaaaaa 519 72 529 DNA Homo sapiens CDS (100)..(492) 72 atataactat ctattcgatg atgaagatac cccaccaaac ccaaaaaaag agatctctcg 60 aggatccgaa ttcgcggccg cgtcgaccgc gccgccaca atg gtg cgc atg aat 114 Met Val Arg Met Asn 1 5 gtc ctg gca gat gct ctc aag agt atc aac aat gcc gaa aag aga ggc 162 Val Leu Ala Asp Ala Leu Lys Ser Ile Asn Asn Ala Glu Lys Arg Gly 10 15 20 aaa cgc cag gtg ctt att agg ccg tgc tcc aaa gtc atc gtc cgg ttt 210 Lys Arg Gln Val Leu Ile Arg Pro Cys Ser Lys Val Ile Val Arg Phe 25 30 35 ctc act gtg atg atg aag cat ggt tac att ggc gaa ttt gaa atc att 258 Leu Thr Val Met Met Lys His Gly Tyr Ile Gly Glu Phe Glu Ile Ile 40 45 50 gat gac cac aga gct ggg aaa att gtt gtg aac ctc aca ggc agg cta 306 Asp Asp His Arg Ala Gly Lys Ile Val Val Asn Leu Thr Gly Arg Leu 55 60 65 aac aag tgt ggg gtg atc agc ccc aga ttt gac gtg caa ctc aaa gac 354 Asn Lys Cys Gly Val Ile Ser Pro Arg Phe Asp Val Gln Leu Lys Asp 70 75 80 85 ctg gaa aaa tgg cag aat aat ctg ctt cca tcc cgc cag ttt ggt ttc 402 Leu Glu Lys Trp Gln Asn Asn Leu Leu Pro Ser Arg Gln Phe Gly Phe 90 95 100 att gta ctg aca acc tca gct ggc atc atg gac cat gaa gaa gca aga 450 Ile Val Leu Thr Thr Ser Ala Gly Ile Met Asp His Glu Glu Ala Arg 105 110 115 cga aaa cac aca gga ggg aaa atc ctg gga ttc ttt ttc tag ggatgta 499 Arg Lys His Thr Gly Gly Lys Ile Leu Gly Phe Phe Phe * 120 125 130 atacatatat ttacaaataa aaaaaaaaaa 529 73 690 DNA Homo sapiens CDS (97)..(507) 73 cgtgacagcg ccggaattcc cgggtcgacc cacgcgtccg ctgggattcc cagctgtttc 60 tgcttgctga tcaggactgc acacagagaa ctcacc atg gag ttt ggg ctg agc 114 Met Glu Phe Gly Leu Ser 1 5 tgg gtt ttc ctt gtt gct att tta aaa ggt gtc cag tgt gag gtg cag 162 Trp Val Phe Leu Val Ala Ile Leu Lys Gly Val Gln Cys Glu Val Gln 10 15 20 ctg gtg gag tcc ggg gga ggc tta gtt cag cct ggg ggg tcc ctg aga 210 Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg 25 30 35 ctc tcc tgt gca gcc tct gga ttc acc ttc agt agc tac tgg atg cac 258 Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Ser Tyr Trp Met His 40 45 50 tgg gtc cgc caa gct cca ggg aag ggg ctg gtg tgg gtc tca cgt att 306 Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Val Trp Val Ser Arg Ile 55 60 65 70 aat agt gat ggg agt agc aca agc tac gcg gac tcc gtg aag ggc cga 354 Asn Ser Asp Gly Ser Ser Thr Ser Tyr Ala Asp Ser Val Lys Gly Arg 75 80 85 ttc acc atc tcc aga gac aac gcc aag aac acg ctg tat ctg caa atg 402 Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Leu Tyr Leu Gln Met 90 95 100 aac agt ctg aga gcc gag gac acg gct gtg tat tac tgt gca aga gac 450 Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp 105 110 115 aca gtg agg gga agt caa tgt gag ccc aga cac aaa cct cgc tgc agg 498 Thr Val Arg Gly Ser Gln Cys Glu Pro Arg His Lys Pro Arg Cys Arg 120 125 130 ggc atc tga gaccacg agggggtgtc ctgggccctg tgaactgggc tgctctccgt 554 Gly Ile * 135 ggcagcggct ggtggtgcta aaggctgatt ttctctcagc atctggggct gattcatcaa 614 gtttcctcag agaacctttc agatttacaa ttctgtactt acgtttaatg tctctgaatg 674 tgacaaaaaa aaaaaa 690 74 4626 DNA Homo sapiens CDS (208)..(1539) 74 ctcgcctgca ctaccggtcc ggaattcccg ggtcgacgat ttcgtgccag gaggcagggg 60 aggctcggcg accctgtcag gcgctgcggg acgccgagga ctggggcggc gtgctggaga 120 tccgcggcca accgtggggt gctgctgtcg ggactcatag gtgtcgtctc ctggaagagg 180 cctctctccc ttgtgataac ctttttc atg ctg ctt tct gca gtg tgt gta 231 Met Leu Leu Ser Ala Val Cys Val 1 5 atg ctg aat ttg gct ggt tca att ctc tct tgt cag aat gct cag cta 279 Met Leu Asn Leu Ala Gly Ser Ile Leu Ser Cys Gln Asn Ala Gln Leu 10 15 20 gtc aac tcc cta gaa ggc tgc cag ttg att aag ttt gac agt gtg gag 327 Val Asn Ser Leu Glu Gly Cys Gln Leu Ile Lys Phe Asp Ser Val Glu 25 30 35 40 gtg tgt gtc tgc tgt gag ctg cag cac cag tcg tcc ggc tgc agc aac 375 Val Cys Val Cys Cys Glu Leu Gln His Gln Ser Ser Gly Cys Ser Asn 45 50 55 ctc ggg gag acg ctg aag ctg aac ccg ctg cag gag aac tgc aac gct 423 Leu Gly Glu Thr Leu Lys Leu Asn Pro Leu Gln Glu Asn Cys Asn Ala 60 65 70 gtg agg ctg acc ttg aag gat ctc ctc ttc agc gtg tgt gcc ctc aac 471 Val Arg Leu Thr Leu Lys Asp Leu Leu Phe Ser Val Cys Ala Leu Asn 75 80 85 gtc ctg tcc act atc gtg tgt gcg ctg gcc aca gcc atg tgc tgt atg 519 Val Leu Ser Thr Ile Val Cys Ala Leu Ala Thr Ala Met Cys Cys Met 90 95 100 cag atg gtc tcc tcc gat gtc ctg cag atg ttc ctt ccg cag agg tca 567 Gln Met Val Ser Ser Asp Val Leu Gln Met Phe Leu Pro Gln Arg Ser 105 110 115 120 cat cct gcc aac ccc acc tgc gtg act cct cac ggc acc gtt ctc cac 615 His Pro Ala Asn Pro Thr Cys Val Thr Pro His Gly Thr Val Leu His 125 130 135 cag acc ctg gat ttc gac gag ttc atc ccc cca ctc ccg cct cca ccc 663 Gln Thr Leu Asp Phe Asp Glu Phe Ile Pro Pro Leu Pro Pro Pro Pro 140 145 150 tat tac ccc cca gag tac acc tgc aca ccg tcc act gag gcc cag agg 711 Tyr Tyr Pro Pro Glu Tyr Thr Cys Thr Pro Ser Thr Glu Ala Gln Arg 155 160 165 ggc ctc cac ctg gac ttt gct ccg tct cca ttc ggc act ttg tat gac 759 Gly Leu His Leu Asp Phe Ala Pro Ser Pro Phe Gly Thr Leu Tyr Asp 170 175 180 gtg gcc atc aat agc ccc ggc ctg ctc tat cct gct gag ctc ccc cct 807 Val Ala Ile Asn Ser Pro Gly Leu Leu Tyr Pro Ala Glu Leu Pro Pro 185 190 195 200 ccg tac gag gcg gtg gtg ggc cag ccc cct gcc agc cag gtt aca agt 855 Pro Tyr Glu Ala Val Val Gly Gln Pro Pro Ala Ser Gln Val Thr Ser 205 210 215 ata ggt cag cag gtg gcc gag tcc agc tcc ggg gac cca aac acc agt 903 Ile Gly Gln Gln Val Ala Glu Ser Ser Ser Gly Asp Pro Asn Thr Ser 220 225 230 gct ggc ttc agc act cca gta cca gct gac agc aca agc ctc ctg gtg 951 Ala Gly Phe Ser Thr Pro Val Pro Ala Asp Ser Thr Ser Leu Leu Val 235 240 245 tcc gag ggc act gct acg cca ggt tcc agc cca tcc ccc gat ggc cct 999 Ser Glu Gly Thr Ala Thr Pro Gly Ser Ser Pro Ser Pro Asp Gly Pro 250 255 260 gtg ggc gcc cca gca ccc tcc gaa cct gcc ctt ccc cct ggc cgc gtg 1047 Val Gly Ala Pro Ala Pro Ser Glu Pro Ala Leu Pro Pro Gly Arg Val 265 270 275 280 tct cca gag gat cct ggc atg ggc tca cag gtg cag cca ggt ccc ggg 1095 Ser Pro Glu Asp Pro Gly Met Gly Ser Gln Val Gln Pro Gly Pro Gly 285 290 295 cat gtg tcc cgc tcc acc agc gac ccc acc ttg tgc aca tct agc atg 1143 His Val Ser Arg Ser Thr Ser Asp Pro Thr Leu Cys Thr Ser Ser Met 300 305 310 gca ggc gat gcc tct tca cac agg ccg tcg tgt agc cag gac ctg gaa 1191 Ala Gly Asp Ala Ser Ser His Arg Pro Ser Cys Ser Gln Asp Leu Glu 315 320 325 gcg gga ctg tct gag gct gtg cct ggg agc gct tcc atg tct cgc tct 1239 Ala Gly Leu Ser Glu Ala Val Pro Gly Ser Ala Ser Met Ser Arg Ser 330 335 340 gcc acg gct gcc tgt cgg gcc cag ctt tca cca gcg ggg gac cca gat 1287 Ala Thr Ala Ala Cys Arg Ala Gln Leu Ser Pro Ala Gly Asp Pro Asp 345 350 355 360 acc tgg aaa act gac caa cgg cca aca cca gag ccc ttc cca gcg acc 1335 Thr Trp Lys Thr Asp Gln Arg Pro Thr Pro Glu Pro Phe Pro Ala Thr 365 370 375 tcc aaa gag cgg cca cgc tct tta gtg gac agc aag gcc tat gcg gac 1383 Ser Lys Glu Arg Pro Arg Ser Leu Val Asp Ser Lys Ala Tyr Ala Asp 380 385 390 gcc agg gtt ttg gtg gcc aag ttt ttg gaa cac tca cac tgt gcc ctc 1431 Ala Arg Val Leu Val Ala Lys Phe Leu Glu His Ser His Cys Ala Leu 395 400 405 ccc acc gag gca cag cac atg gtg ggt gcc atg cgc ttg gct gtc acc 1479 Pro Thr Glu Ala Gln His Met Val Gly Ala Met Arg Leu Ala Val Thr 410 415 420 aac gag gag cgc ctc gag gag gag gcc gtc ttc ggc gct gat gtt ctg 1527 Asn Glu Glu Arg Leu Glu Glu Glu Ala Val Phe Gly Ala Asp Val Leu 425 430 435 440 gac cag gta tga agg agccacattt ctgaccgtgg acaccaacgc ctggcgccac 1582 Asp Gln Val * agatgttctt ggcagaagcc atcatgcctg acaaagaggc cttcaggccc agcttggcgg 1642 aggataaatg tgggggggac acccaggatg atctgggggc ggtgtgggca gggaactgtt 1702 accccctctc tcgaggggag ccgagcagtg tctctttggg gattgcattt cctgcctagc 1762 ccagtaattc ggaaagatga ctttcacgtc cacagtgaac tctctggttt tatctggcgt 1822 gcagcacctt gaactgagca gtgttgcaca aatgtgaata cagcaacagg cgacacttac 1882 gtcacctaaa gactcaaagt atctccaaaa tcagggcctt ccaaagcagg agtctcccat 1942 cccccattta acttagtgtt cagtggacag agggtgacat cgagtcatga aacattttct 2002 catgtggctc gatggctcta tcattaggcg ttcatcacgc tctggcctat ttcctgtgaa 2062 aggaaatagg tagtgttagc acagatggca gcctgggccc aactttctgt ccacagggct 2122 attgtgcaaa caaatgtgca gtgcgggcct ctgccatagc ccggcccccc ccagggaaca 2182 ggccggtgtt gcgggggttg gaggaaccca ccatctcttg ggccttgagc tcggcctccc 2242 tccgtggggt gccttccccc cctcctcttg ggcccccttt ctccaggctc ccatcctgtc 2302 cctggagcag ttgtgtgatc cgtaacaaca agtgccgatt cccagctcct ttgtgtctga 2362 gctcacttga ttgagctcag cgggtcacag ttctgcagga gagaggccgg tttctctgag 2422 aagtagcccc tcctgataaa gcaggtccct ttgacccaga gctgaccttt ccccgggcat 2482 gcggcagcag acacacctgc gcaggaggat cataaaccac ttacaaaccc acgcgagaag 2542 ggaagcagac acccaacgtg ctgcttatgg agaagcagac acgcccagct tggggacagc 2602 ctggggacct tggactttct tagcccccat ccccttgttt tctggtggca tcagtggcag 2662 ctgctcccaa caatggccgt ggaacagcgc catccacgag aactttgtgc agtgatggaa 2722 atgcctgttc agggccacta gcagccacag cccctgagct gcgttgggtg ggccctgcgg 2782 tgaacaaaac agcctagagg ccaaggtctc cccagagagc ccatgagcct ggcatggggg 2842 cacaggggga ccagagggtg tcttccactc ctgggtgcca gggcaggggg ctcacgctgc 2902 tgttccctcg gctttgtggg gcttgtcctt gagctccccc aattccctaa tgccactgtg 2962 gccagtgtgc tggggagctt ctgtgtggct ggaagctggg aagggggtga ggttccaatc 3022 caggtgccca gagccttcct ccagtccttt atccctgccc tgggggctgc ggtgtgggac 3082 tccttcagct gtggtcggct gaaaaggctt cgattgcttt agagagctga aaacacataa 3142 gccaggcctt ttgatgacaa cctgcacttt tgcaggagag acgtactaga gatgaatttt 3202 tgagcacttt attcagacta taaaacagga aatctctaat tttcctcaag tgggggcttt 3262 tgaattccct caaggcaagt ccctttgcag gtgaaattaa ttggtggatt ttcagaatgg 3322 ccgccctgga gccgagcttc agccacgcct gacgccctgg cctctgaatc tccactgtct 3382 ctgaggtgcg ctggggccac accgcagggg tttcacctgc ttgggggggt ccacactagg 3442 gcttgggggt tcacacagca ttgtccctgg gctgagccct tgggtgggct agagctgcag 3502 tcctcagaca tggctgcaat tccagcgagg ccaagaccac cagccaccca gtggacttcg 3562 ggtctctggg gtgttctcct catgcagccg gggcagaggc ctactggacc ccctcagcct 3622 gctgctcagc atccttccct tctctgcagc agggcccggt cccaatggcc aatggggctg 3682 ctgccccagc agtgcctccc tgcgggcccc tcacctgcac cccaccttca cccagctctg 3742 ggtttgcgct ggtggcagct ctgttttgtg gatacggaaa ctgtacccaa cttgatgccg 3802 ctgggctgga accttctgcc ccttcgaaat gaggcagtca gggacggggt ggggtgcccc 3862 catcagcccc gctgctcagg gccactcatg gactctagga gggtccaggt tctgggcttc 3922 ctgggaaggt ccccagaaga gagaggtgct ggtagactag ggaatgtgct ggcaacttga 3982 cccagcagct gtggtcccct tggccccggc tccacggtat ccgggtacca gcagcaagag 4042 cccaggcccc gggctgcacg tcagctcaca gcccaggaga aagctggctg cttcccctcc 4102 ctatgcgtct ttcccccgct ccaatcatgc tccctctggg atctgaaatg ggccaactgt 4162 ggctgctttg ggggtgacac gctccttctc caactcagct gggccccggg catcccctgc 4222 cctcccctga gacccaaagg gggttggcac ctgctgtgac accaccgttg accccagcct 4282 gggggccaca aggttgctga gtggggagaa catggacccc aactctatgg caagcaagat 4342 cgcagaaggg ggagcatcat ccgcaaggac ttcaggtctc ccttggctgg agatgaggat 4402 ccacattaaa tgtttgtaac acaccaggcc acagaaagct cgctacacac agatgcttct 4462 ccccacccat gctgactctc agaggctgct aaggcagaat ttataggaaa ttgttttcaa 4522 gccaccagag acctgtctgt acaactggaa aggctgtatt tatttaatgt acctcaaggt 4582 gttttaataa tgatccgtgt tttaataaaa agaagtattt ctgg 4626 75 1529 DNA Homo sapiens CDS (1)..(1395) 75 atg ccg gcc acc tgg gaa gac ttt aag cag ata ata aag tgt gaa ata 48 Met Pro Ala Thr Trp Glu Asp Phe Lys Gln Ile Ile Lys Cys Glu Ile 1 5 10 15 aca gtt att tat aga cat ggc ctt ccc ttg gta aca ctt acc ttg cca 96 Thr Val Ile Tyr Arg His Gly Leu Pro Leu Val Thr Leu Thr Leu Pro 20 25 30 tct aga aaa gaa cgt tgt caa ttc gta gtc aaa cca atg ttg tca aca 144 Ser Arg Lys Glu Arg Cys Gln Phe Val Val Lys Pro Met Leu Ser Thr 35 40 45 gtt ggt tca ttc ctt cag gac cta caa aat gaa gat aag ggt atc aaa 192 Val Gly Ser Phe Leu Gln Asp Leu Gln Asn Glu Asp Lys Gly Ile Lys 50 55 60 act gca gcc atc ttc aca gca gtt tat tca cct act gaa gga cat ctg 240 Thr Ala Ala Ile Phe Thr Ala Val Tyr Ser Pro Thr Glu Gly His Leu 65 70 75 80 gga tac ttc caa gtt ttg gca att atg aat gga gtt gct ata aat aca 288 Gly Tyr Phe Gln Val Leu Ala Ile Met Asn Gly Val Ala Ile Asn Thr 85 90 95 cat gcg cag gct ttt gtt tgc acg gag att ctt caa gca atc act atg 336 His Ala Gln Ala Phe Val Cys Thr Glu Ile Leu Gln Ala Ile Thr Met 100 105 110 tca gca gac aca ggt gtt tct ctt cct tca tat gag gaa tat cag gga 384 Ser Ala Asp Thr Gly Val Ser Leu Pro Ser Tyr Glu Glu Tyr Gln Gly 115 120 125 tcc aaa ctt att cga aaa gct aaa gag gca cca ttc gta ccc att gga 432 Ser Lys Leu Ile Arg Lys Ala Lys Glu Ala Pro Phe Val Pro Ile Gly 130 135 140 ata gca ggt ttt gca gca gtt gtt gca tat gga tta cac aaa ctg aag 480 Ile Ala Gly Phe Ala Ala Val Val Ala Tyr Gly Leu His Lys Leu Lys 145 150 155 160 agc agg gga aat act aaa atg tcc att cat ctg atc cac atg cgt gtg 528 Ser Arg Gly Asn Thr Lys Met Ser Ile His Leu Ile His Met Arg Val 165 170 175 gta gcc caa ggc ttt gtt gta gga gca atg act gtt ggt tct ctt aac 576 Val Ala Gln Gly Phe Val Val Gly Ala Met Thr Val Gly Ser Leu Asn 180 185 190 agt gat aat gaa caa tta cag ctc tca gaa ggg tat caa tct gag gga 624 Ser Asp Asn Glu Gln Leu Gln Leu Ser Glu Gly Tyr Gln Ser Glu Gly 195 200 205 ctt ctc ata gca gag cct aat ttt ata tgg act tat aaa ccc atg gag 672 Leu Leu Ile Ala Glu Pro Asn Phe Ile Trp Thr Tyr Lys Pro Met Glu 210 215 220 gag gca ctt agc cgt gca gga aca aat ggc aag cct tta gcc cga tct 720 Glu Ala Leu Ser Arg Ala Gly Thr Asn Gly Lys Pro Leu Ala Arg Ser 225 230 235 240 gga gcg gca aag ggg tgc ctc gct gga tca gga gca cag tgg aca ccc 768 Gly Ala Ala Lys Gly Cys Leu Ala Gly Ser Gly Ala Gln Trp Thr Pro 245 250 255 tgc tgg atc cgg aag aat gta agt cag cag cga gtc tgc tac ggc ggc 816 Cys Trp Ile Arg Lys Asn Val Ser Gln Gln Arg Val Cys Tyr Gly Gly 260 265 270 aaa aca gca gtg gtg gac aaa aaa cca agt aat gag cac act gct gag 864 Lys Thr Ala Val Val Asp Lys Lys Pro Ser Asn Glu His Thr Ala Glu 275 280 285 atg gaa cac atg aaa tct ttg gtt cac aga cta ttt aca atc ttg cat 912 Met Glu His Met Lys Ser Leu Val His Arg Leu Phe Thr Ile Leu His 290 295 300 tta gaa gag tct cag aaa aag aga gag cac cat tta ctg gag aaa att 960 Leu Glu Glu Ser Gln Lys Lys Arg Glu His His Leu Leu Glu Lys Ile 305 310 315 320 gac cac ctg aag gaa cag ctg cag ccc ctt gaa cag gtg aaa gct gga 1008 Asp His Leu Lys Glu Gln Leu Gln Pro Leu Glu Gln Val Lys Ala Gly 325 330 335 ata gaa gct cat tcg gaa gcc aaa acc agt gga ctc ctg tgg gct gga 1056 Ile Glu Ala His Ser Glu Ala Lys Thr Ser Gly Leu Leu Trp Ala Gly 340 345 350 ttg gca ctg ctg tcc att cag ggt ggg gca ctg gcc tgg ctc acg tgg 1104 Leu Ala Leu Leu Ser Ile Gln Gly Gly Ala Leu Ala Trp Leu Thr Trp 355 360 365 tgg gtg tac tcc tgg gat atc atg gag cca gtt aca tac ttc atc aca 1152 Trp Val Tyr Ser Trp Asp Ile Met Glu Pro Val Thr Tyr Phe Ile Thr 370 375 380 ttt gca aat tct atg gtc ttt ttt gca tac ttt ata gtc act cga cag 1200 Phe Ala Asn Ser Met Val Phe Phe Ala Tyr Phe Ile Val Thr Arg Gln 385 390 395 400 gat tat act tac tca gct gtt aag agt agg caa ttt ctt cag ttc ttc 1248 Asp Tyr Thr Tyr Ser Ala Val Lys Ser Arg Gln Phe Leu Gln Phe Phe 405 410 415 cac aag aaa tca aag caa cag cac ttt gat gtg cag caa tac aac aag 1296 His Lys Lys Ser Lys Gln Gln His Phe Asp Val Gln Gln Tyr Asn Lys 420 425 430 tta aaa gaa gac ctt gct aag gct aaa gaa tcc ctg aaa cag gcg cgt 1344 Leu Lys Glu Asp Leu Ala Lys Ala Lys Glu Ser Leu Lys Gln Ala Arg 435 440 445 cat tct ctc tgt ttg caa atg caa gta gaa gaa ctc aat gaa aag aat 1392 His Ser Leu Cys Leu Gln Met Gln Val Glu Glu Leu Asn Glu Lys Asn 450 455 460 taa tctt acagttttaa atgtcgtcag attttccatt atgtattgat tttgcaactt 1449 * 465 aggatgtttt tgagtcccat ggttcatttt gattgtttaa tctttgttat taaattcttg 1509 taaaacagaa aaaaaaaaaa 1529 76 2101 DNA Homo sapiens CDS (121)..(1332) 76 atttggccct cgaggccaag aattcggcac gagcggagcc aagacggtcg gggctgcttg 60 ctaactccag gaacaggttt aagtttttga aactgaagta ggtctacaca gtaggaactc 120 atg tca ttt ctt acc aat gat gcg agc tca gag tca ata gca tcc ttc 168 Met Ser Phe Leu Thr Asn Asp Ala Ser Ser Glu Ser Ile Ala Ser Phe 1 5 10 15 tct aaa cag gag gtc atg agt agc ttt ctg cca gag gga ggg tgt tac 216 Ser Lys Gln Glu Val Met Ser Ser Phe Leu Pro Glu Gly Gly Cys Tyr 20 25 30 gag ctg ctc act gtg ata ggc aaa gga ttt gag gac ctg atg act gtg 264 Glu Leu Leu Thr Val Ile Gly Lys Gly Phe Glu Asp Leu Met Thr Val 35 40 45 aat cta gca agg tac aaa cca aca gga gag tac gtg act gta cgg agg 312 Asn Leu Ala Arg Tyr Lys Pro Thr Gly Glu Tyr Val Thr Val Arg Arg 50 55 60 att aac cta gaa gct tgt tcc aat gag atg gta aca ttc ttg cag ggc 360 Ile Asn Leu Glu Ala Cys Ser Asn Glu Met Val Thr Phe Leu Gln Gly 65 70 75 80 gag ctg cat gtc tcc aaa ctc ttc aac cat ccc aat atc gtg cca tat 408 Glu Leu His Val Ser Lys Leu Phe Asn His Pro Asn Ile Val Pro Tyr 85 90 95 cga gcc act ttt att gca gac aat gag ctg tgg gtt gtc aca tca ttc 456 Arg Ala Thr Phe Ile Ala Asp Asn Glu Leu Trp Val Val Thr Ser Phe 100 105 110 atg gca tac ggt tct gca aaa gat ctc atc tgt aca cac ttc atg gat 504 Met Ala Tyr Gly Ser Ala Lys Asp Leu Ile Cys Thr His Phe Met Asp 115 120 125 ggc atg aat gag ctg gcg att gct tac atc ctg cag ggg gtg ctg aag 552 Gly Met Asn Glu Leu Ala Ile Ala Tyr Ile Leu Gln Gly Val Leu Lys 130 135 140 gcc ctc gac tac atc cac cac atg gga tat gta cac agg agt gtc aaa 600 Ala Leu Asp Tyr Ile His His Met Gly Tyr Val His Arg Ser Val Lys 145 150 155 160 gcc agc cac atc ctg atc tct gtg gat ggg aag gtc tac ctg tct ggt 648 Ala Ser His Ile Leu Ile Ser Val Asp Gly Lys Val Tyr Leu Ser Gly 165 170 175 ttg cgc agc aac ctc agc atg ata agc cat ggg cag cgg cag cga gtg 696 Leu Arg Ser Asn Leu Ser Met Ile Ser His Gly Gln Arg Gln Arg Val 180 185 190 gtc cac gat ttt ccc aag tac agt gtc aag gtt ctg ccg tgg ctc agc 744 Val His Asp Phe Pro Lys Tyr Ser Val Lys Val Leu Pro Trp Leu Ser 195 200 205 ccc gag gtc ctc cag cag aat ctc cag ggt tat gat gcc aag tct gac 792 Pro Glu Val Leu Gln Gln Asn Leu Gln Gly Tyr Asp Ala Lys Ser Asp 210 215 220 atc tac agt gtg gga atc aca gcc tgt gaa ctg gcc aac ggc cat gtc 840 Ile Tyr Ser Val Gly Ile Thr Ala Cys Glu Leu Ala Asn Gly His Val 225 230 235 240 ccc ttt aag gat atg cct gcc acc cag ccc agg tcc tgg ttc tgt cct 888 Pro Phe Lys Asp Met Pro Ala Thr Gln Pro Arg Ser Trp Phe Cys Pro 245 250 255 ccc cag atg ctg cta gag aaa ctg aac ggc aca gtg ccc tgc ctg ttg 936 Pro Gln Met Leu Leu Glu Lys Leu Asn Gly Thr Val Pro Cys Leu Leu 260 265 270 gat acc agc acc atc ccc gct gag gag ctg acc atg agc cct tcg cgc 984 Asp Thr Ser Thr Ile Pro Ala Glu Glu Leu Thr Met Ser Pro Ser Arg 275 280 285 tca gtg gcc aac tct ggc ctg agt gac agc ctg acc acc agc acc ccc 1032 Ser Val Ala Asn Ser Gly Leu Ser Asp Ser Leu Thr Thr Ser Thr Pro 290 295 300 cgg ccc tcc aac ggt gac tcg ccc tcc cac ccc tac cac cga acc ttc 1080 Arg Pro Ser Asn Gly Asp Ser Pro Ser His Pro Tyr His Arg Thr Phe 305 310 315 320 tcc ccc cac ttc cac cac ttt gtg gag cag tgc ctt cag cgc aac ccg 1128 Ser Pro His Phe His His Phe Val Glu Gln Cys Leu Gln Arg Asn Pro 325 330 335 gat gcc agg ccc agt gcc agc acc ctc ctg aac cac tct ttc ttc aag 1176 Asp Ala Arg Pro Ser Ala Ser Thr Leu Leu Asn His Ser Phe Phe Lys 340 345 350 cag atc aag cga cgt gcc tca gag gct ttg ccc gaa ttg ctt cgt cct 1224 Gln Ile Lys Arg Arg Ala Ser Glu Ala Leu Pro Glu Leu Leu Arg Pro 355 360 365 gtc acc ccc atc acc aat ttt gag ggc agc cag tct cag gac cac agt 1272 Val Thr Pro Ile Thr Asn Phe Glu Gly Ser Gln Ser Gln Asp His Ser 370 375 380 gga atc ttt ggc ctg gta aca aac ctg gaa gag ctg gag gtg gac gat 1320 Gly Ile Phe Gly Leu Val Thr Asn Leu Glu Glu Leu Glu Val Asp Asp 385 390 395 400 tgg gag ttc tga gcc tctgcaaact gtgcgcattc tccagccagg gatgcagagg 1375 Trp Glu Phe * ccacccagag gcccttcctg agggccggcc acattcccgc cctcctgggc agattgggta 1435 gaaaggacat tcttccagga aagttgactg ctgactgatt gggaaagaaa atcctggaga 1495 gatacttcac tgctccaagg cttttgagac acaagggaat ctcaacaacc agggatcagg 1555 agggtccaaa gccgacattc ccagtcctgt gagctcaggt gacctcctcc gcagaagaga 1615 gatgctgctc tggccctggg agctgaattc caagcccagg gtttggctcc ttaaacccga 1675 ggaccgccac ctcttcccag tgcttgcgac cagcctcatt ctatttaact ttgctctcag 1735 atgcctcaga tgctataggt cagtgaaagg gcaagtagta agctgcctgc ctcccttccc 1795 tcagacctct ccctcataat tccagagaag ggcatttctg tctttttaag cacagactaa 1855 ggctggaaca gtccatcctt atccctcttc tggcttgggc cctgacacct aagtctttcc 1915 cacggtttat gtgtgtgcct cattcctttc ccaccaagaa tccatcttag cgcctcctgc 1975 cagctgccct ggtgctttct ccaagggcca tcagtgtctt gcctagcttg agggcttaag 2035 tccttatgct gtgttagttt cgttgtcaga acaaattaaa attttcagag acgcaaaaaa 2095 aaaaaa 2101 77 4581 DNA Homo sapiens CDS (345)..(3221) 77 agcacgtacc ggtccggaat tcccgggtcg acgatttcgt cttcaagggg acaaaaagag 60 agctagaaaa aataggggga gggggtcata ttgattcctg tgggagatga aattcggata 120 ttaaacaact gacctaagtc gcttacagtt cttcctccca cctttctatt ttgcctctta 180 atcagcccag gcgtcctttc cctgagatta aaaaaaagag agaggggagc gttaacaatt 240 aaatgtaata agcaactcca aagatgggga tgctgtcgag gtggtagttc cgtgcaaacc 300 ttgctattac cgttgcaaat agacgcggag cccaaggagg taaa atg cac act tgc 356 Met His Thr Cys 1 tgc ccc cca gta act ttg gaa cag gac ctt cac aga aaa atg cat agc 404 Cys Pro Pro Val Thr Leu Glu Gln Asp Leu His Arg Lys Met His Ser 5 10 15 20 tgg atg ctg cag act cta gcg ttt gct gta aca tct ctc gtc ctt tcg 452 Trp Met Leu Gln Thr Leu Ala Phe Ala Val Thr Ser Leu Val Leu Ser 25 30 35 tgt gca gaa acc atc gat tat tat ggg gaa atc tgt gac aat gca tgt 500 Cys Ala Glu Thr Ile Asp Tyr Tyr Gly Glu Ile Cys Asp Asn Ala Cys 40 45 50 cct tgt gag gaa aag gac ggc att tta act gtg agc tgt gaa aac cgg 548 Pro Cys Glu Glu Lys Asp Gly Ile Leu Thr Val Ser Cys Glu Asn Arg 55 60 65 ggg atc atc agt ctc tct gaa att agc cct ccc cgt ttc cca atc tac 596 Gly Ile Ile Ser Leu Ser Glu Ile Ser Pro Pro Arg Phe Pro Ile Tyr 70 75 80 cac ctc ttg ttg tcc gga aac ctt ttg aac cgt ctc tat ccc aat gag 644 His Leu Leu Leu Ser Gly Asn Leu Leu Asn Arg Leu Tyr Pro Asn Glu 85 90 95 100 ttt gtc aat tac act ggg gct tca att ttg cat cta ggt agc aat gtt 692 Phe Val Asn Tyr Thr Gly Ala Ser Ile Leu His Leu Gly Ser Asn Val 105 110 115 atc cag gac att gag acc ggg gct ttc cat ggg cta cgg ggt ttg agg 740 Ile Gln Asp Ile Glu Thr Gly Ala Phe His Gly Leu Arg Gly Leu Arg 120 125 130 aga ttg cat cta aac aat aat aaa ctg gaa ctt ctg cga gat gat acc 788 Arg Leu His Leu Asn Asn Asn Lys Leu Glu Leu Leu Arg Asp Asp Thr 135 140 145 ttc ctt ggc ttg gag aac ctg gag tac cta cag gtc gat tac aac tac 836 Phe Leu Gly Leu Glu Asn Leu Glu Tyr Leu Gln Val Asp Tyr Asn Tyr 150 155 160 atc agc gtc att gaa ccc aat gct ttt ggg aaa ctg cat ttg ttg cag 884 Ile Ser Val Ile Glu Pro Asn Ala Phe Gly Lys Leu His Leu Leu Gln 165 170 175 180 gtg ctt atc ctc aat gac aat ctt ttg tcc agt tta ccc aac aat ctt 932 Val Leu Ile Leu Asn Asp Asn Leu Leu Ser Ser Leu Pro Asn Asn Leu 185 190 195 ttc cgt ttt gtg ccc tta acg cac ttg gac ctc cgg ggg aac cgg ctg 980 Phe Arg Phe Val Pro Leu Thr His Leu Asp Leu Arg Gly Asn Arg Leu 200 205 210 aaa ctt ctg ccc tac gtg ggg ctc ttg cag cac atg gat aaa gtt gtg 1028 Lys Leu Leu Pro Tyr Val Gly Leu Leu Gln His Met Asp Lys Val Val 215 220 225 gag cta cag ctg gag gaa aac cct tgg aat tgt tct tgt gag ctg atc 1076 Glu Leu Gln Leu Glu Glu Asn Pro Trp Asn Cys Ser Cys Glu Leu Ile 230 235 240 tct cta aag gat tgg ttg gac agc atc tcc tat tca gcc ctg gtg ggg 1124 Ser Leu Lys Asp Trp Leu Asp Ser Ile Ser Tyr Ser Ala Leu Val Gly 245 250 255 260 gat gta gtt tgt gag acc ccc ttc cgc tta cac gga agg gac ttg gac 1172 Asp Val Val Cys Glu Thr Pro Phe Arg Leu His Gly Arg Asp Leu Asp 265 270 275 gag gta tcc aag cag gaa ctt tgc cca agg aga ctt att tct gac tac 1220 Glu Val Ser Lys Gln Glu Leu Cys Pro Arg Arg Leu Ile Ser Asp Tyr 280 285 290 gag atg agg ccg cag acg cct ttg agc acc acg ggg tat tta cac acc 1268 Glu Met Arg Pro Gln Thr Pro Leu Ser Thr Thr Gly Tyr Leu His Thr 295 300 305 acc ccg gcg tca gtg aat tct gtg gcc act tct tcc tct gct gtt tac 1316 Thr Pro Ala Ser Val Asn Ser Val Ala Thr Ser Ser Ser Ala Val Tyr 310 315 320 aaa ccc cct ttg aag ccc cct aag ggg act cgc caa ccc aac aag ccc 1364 Lys Pro Pro Leu Lys Pro Pro Lys Gly Thr Arg Gln Pro Asn Lys Pro 325 330 335 340 agg gtg cgc ccc acc tct cgg cag ccc tct aag gac ttg ggc tac agc 1412 Arg Val Arg Pro Thr Ser Arg Gln Pro Ser Lys Asp Leu Gly Tyr Ser 345 350 355 aac tat ggc ccc agc atc gcc tat cag acc aaa tcc ccg gtg cct ttg 1460 Asn Tyr Gly Pro Ser Ile Ala Tyr Gln Thr Lys Ser Pro Val Pro Leu 360 365 370 gag tgt ccc acc gcg tgc tct tgc aac ctg cag atc tct gat ctg ggc 1508 Glu Cys Pro Thr Ala Cys Ser Cys Asn Leu Gln Ile Ser Asp Leu Gly 375 380 385 ctc aac gta aac tgc cag gag cga aag atc gag agc atc gct gaa ctg 1556 Leu Asn Val Asn Cys Gln Glu Arg Lys Ile Glu Ser Ile Ala Glu Leu 390 395 400 cag ccc aag ccc tac aat ccc aag aaa atg tat ctg aca gag aac tac 1604 Gln Pro Lys Pro Tyr Asn Pro Lys Lys Met Tyr Leu Thr Glu Asn Tyr 405 410 415 420 atc gct gtc gtg cgc agg aca gac ctc ctg gag gcc acg ggg ctg gac 1652 Ile Ala Val Val Arg Arg Thr Asp Leu Leu Glu Ala Thr Gly Leu Asp 425 430 435 ctc ctg cac ctg ggg aat aac cgc atc tcg atg atc cag gac cgc gct 1700 Leu Leu His Leu Gly Asn Asn Arg Ile Ser Met Ile Gln Asp Arg Ala 440 445 450 ttc ggg gat ctc acc aac ctg agg cgc ctc tac ctg aat ggc aac agg 1748 Phe Gly Asp Leu Thr Asn Leu Arg Arg Leu Tyr Leu Asn Gly Asn Arg 455 460 465 atc gag agg ctg agc ccg gag tta ttc tat ggc ctg cag agc ctg cag 1796 Ile Glu Arg Leu Ser Pro Glu Leu Phe Tyr Gly Leu Gln Ser Leu Gln 470 475 480 tat ctc ttc ctc cag tac aat ctc atc cgc gag att cag tct gga act 1844 Tyr Leu Phe Leu Gln Tyr Asn Leu Ile Arg Glu Ile Gln Ser Gly Thr 485 490 495 500 ttt gac ccg gtc cca aac ctc cag ctg cta ttc ttg aat aac aac ctc 1892 Phe Asp Pro Val Pro Asn Leu Gln Leu Leu Phe Leu Asn Asn Asn Leu 505 510 515 ctg cag gcc atg ccc tca ggc gtc ttc tct ggc ttg acc ctc ctc agg 1940 Leu Gln Ala Met Pro Ser Gly Val Phe Ser Gly Leu Thr Leu Leu Arg 520 525 530 cta aac ctg agg agt aac cac ttc acc tcc ttg cca gtg agt gga gtt 1988 Leu Asn Leu Arg Ser Asn His Phe Thr Ser Leu Pro Val Ser Gly Val 535 540 545 ttg gac cag ctg aag tca ctc atc caa atc gac ctg cat gac aat cct 2036 Leu Asp Gln Leu Lys Ser Leu Ile Gln Ile Asp Leu His Asp Asn Pro 550 555 560 tgg gat tgt acc tgt gac att gtg ggc atg aag ctg tgg gtg gag cag 2084 Trp Asp Cys Thr Cys Asp Ile Val Gly Met Lys Leu Trp Val Glu Gln 565 570 575 580 ctc aaa gtg ggc gtc cta gtg gac gag gtg atc tgt aag gcg ccc aaa 2132 Leu Lys Val Gly Val Leu Val Asp Glu Val Ile Cys Lys Ala Pro Lys 585 590 595 aaa ttc gct gag acc gac atg cgc tcc att aag tcg gag ctg ctg tgc 2180 Lys Phe Ala Glu Thr Asp Met Arg Ser Ile Lys Ser Glu Leu Leu Cys 600 605 610 cct gac tat tca gat gta gta gtt tcc acg ccc aca ccc tcc tct atc 2228 Pro Asp Tyr Ser Asp Val Val Val Ser Thr Pro Thr Pro Ser Ser Ile 615 620 625 cag gtc cct gcg agg acc agc gcc gtg act cct gcg gtc cgg ttg aat 2276 Gln Val Pro Ala Arg Thr Ser Ala Val Thr Pro Ala Val Arg Leu Asn 630 635 640 agc acc ggg gcc ccc gcg agc ttg ggc gca ggc gga ggg gcg tcg tcg 2324 Ser Thr Gly Ala Pro Ala Ser Leu Gly Ala Gly Gly Gly Ala Ser Ser 645 650 655 660 gtg ccc ttg tct gtg tta att ctc agc ctc ctg ctg gtt ttc atc atg 2372 Val Pro Leu Ser Val Leu Ile Leu Ser Leu Leu Leu Val Phe Ile Met 665 670 675 tcc gtc ttc gtg gcc gcc ggg ctc ttc gtg ctg gtc atg aag cgc agg 2420 Ser Val Phe Val Ala Ala Gly Leu Phe Val Leu Val Met Lys Arg Arg 680 685 690 aag aag aac cag agc gac cac acc agc acc aac aac tcc gac gtg agc 2468 Lys Lys Asn Gln Ser Asp His Thr Ser Thr Asn Asn Ser Asp Val Ser 695 700 705 tcc ttt aac atg cag tac agc gtg tac ggc ggc ggc ggc ggc acg ggc 2516 Ser Phe Asn Met Gln Tyr Ser Val Tyr Gly Gly Gly Gly Gly Thr Gly 710 715 720 ggc cac cca cac gcg cac gtg cat cac cgc ggg ccc gcg ctg ccc aag 2564 Gly His Pro His Ala His Val His His Arg Gly Pro Ala Leu Pro Lys 725 730 735 740 gtg aag acg ccc gcg ggc cac gtg tat gaa tac atc ccc cac cca ctg 2612 Val Lys Thr Pro Ala Gly His Val Tyr Glu Tyr Ile Pro His Pro Leu 745 750 755 ggc cac atg tgc aaa aac ccc atc tac cgc tcc cga gag ggc aac tcc 2660 Gly His Met Cys Lys Asn Pro Ile Tyr Arg Ser Arg Glu Gly Asn Ser 760 765 770 gta gag gat tac aaa gac ctg cac gag ctc aag gtc acc tac agc agc 2708 Val Glu Asp Tyr Lys Asp Leu His Glu Leu Lys Val Thr Tyr Ser Ser 775 780 785 aac cac cac ctg cag cag cag cag cag ccg ccg ccg cca ccg cag cag 2756 Asn His His Leu Gln Gln Gln Gln Gln Pro Pro Pro Pro Pro Gln Gln 790 795 800 cca cag cag cag ccc ccg ccg cag ctg cag ctg cag cct ggg gag gag 2804 Pro Gln Gln Gln Pro Pro Pro Gln Leu Gln Leu Gln Pro Gly Glu Glu 805 810 815 820 gag agg cgg gaa agc cac cac ttg cgg agc ccc gcc tac agc gtc agc 2852 Glu Arg Arg Glu Ser His His Leu Arg Ser Pro Ala Tyr Ser Val Ser 825 830 835 acc atc gag ccc cgg gag gac ctg ctg tcg ccg gtg cag gac gcc gac 2900 Thr Ile Glu Pro Arg Glu Asp Leu Leu Ser Pro Val Gln Asp Ala Asp 840 845 850 cgc ttt tac agg ggc att tta gaa cca gac aaa cac tgc tcc acc acc 2948 Arg Phe Tyr Arg Gly Ile Leu Glu Pro Asp Lys His Cys Ser Thr Thr 855 860 865 ccc gcc ggc aat agc ctc ccg gaa tat ccc aaa ttc ccg tgc agc ccc 2996 Pro Ala Gly Asn Ser Leu Pro Glu Tyr Pro Lys Phe Pro Cys Ser Pro 870 875 880 gct gct tac act ttc tcc ccc aac tat gac ctg aga cgc ccc cat cag 3044 Ala Ala Tyr Thr Phe Ser Pro Asn Tyr Asp Leu Arg Arg Pro His Gln 885 890 895 900 tat ttg cac ccg ggg gca ggg gac agc agg cta cgg gaa ccg gtg ctc 3092 Tyr Leu His Pro Gly Ala Gly Asp Ser Arg Leu Arg Glu Pro Val Leu 905 910 915 tac agc ccc ccg agt gct gtc ttt gta gaa ccc aac cgg aac gaa tat 3140 Tyr Ser Pro Pro Ser Ala Val Phe Val Glu Pro Asn Arg Asn Glu Tyr 920 925 930 ctg gag tta aaa gca aaa cta aac gtt gag ccg gac tac ctc gaa gtg 3188 Leu Glu Leu Lys Ala Lys Leu Asn Val Glu Pro Asp Tyr Leu Glu Val 935 940 945 ctg gaa aaa cag acc acg ttt agc cag ttc taa aagcaaag aaactctctt 3239 Leu Glu Lys Gln Thr Thr Phe Ser Gln Phe * 950 955 ggagcttttg catttaaaac aaacaagcaa gcagacacac acagtgaaca catttgatta 3299 attgtgttgt ttcaacgttt agggtgaagt gccttggcac gggatttctc agcttcggtg 3359 gaagatacga aaagggtgtg caatttcctt taaaatttac acgtgggaaa catttgtgta 3419 aactgggcac atcactttct cttcttgcgt gtggggcagg tgtggagaag ggctttaagg 3479 aggccaattt gctgcgcggg tgacctgtga aaggtcacag tcatttttgt agtggttgga 3539 agtgctaaga atggtggatg atggcagagc atagattcta ctcttcctct tttgcttcct 3599 ccccctcccc cgcccctgcc ccacctctct ttctcccctt ttaagccatg ggtgggtcta 3659 actggctttt gtggagaaat tagcacaccc caactttaat aggaaatttg ttctcttttt 3719 ccgcccctct ccttctctcc tcccctcccc tcccttctca ttccttttct ttgtttttaa 3779 aggatgtgtt tggatgcatt ctggacattt gaattaaaaa aaaagtattg tgatcctgta 3839 aaggatcacc atagatgtgg acaaatcatt aaaattacag agctatatga tccataattg 3899 attagtcaaa ataacttatt gatgaaatat acaaatattt tattgtagca cctattttta 3959 tatgcacatt tagcattcct ctttccttca ctatttagcc tatgattttg cagaggtgtc 4019 acactgtatt aggatctgca tttctaaaac tgacgtggta tcaggaaggc attttcaatc 4079 attcaaaatg tggagaattt aatggctaaa tctttaaaag ccaatgcaac ccacccaatt 4139 gaatctgcat tttcttttaa gaaaacagag ctgattgtat cccaatgtat tttaaaaaat 4199 agggcaattg attgggccat tccgagagaa ttgtttgcaa gttttgggtt ttattagaaa 4259 atatttgaaa gtatttttat taatgaacca aaatgacatg ttcatttgac tactattgta 4319 gccgattttc gattgtttaa ccaaacccag ttgcatttgt acagatccac gtgtactggc 4379 acctcagaag accaaatcat ggactgtaca agtctctata caatgtcttt atccctgtgg 4439 gcagcaagca atgatgataa tgacaaacag gatatctgta agatggggct actgttgtta 4499 cagtctcata tgtatcccag cacatgtaat tttttaaata gtttctgaat aaacacttga 4559 taactatgtc aaaaaaaaaa aa 4581 78 1348 DNA Homo sapiens CDS (1)..(1143) 78 atg gtt gat gtc gaa ttc ttt ggc aac ttt tta tgt agt tgt aag cag 48 Met Val Asp Val Glu Phe Phe Gly Asn Phe Leu Cys Ser Cys Lys Gln 1 5 10 15 atc agc ttc aat gat tgt tct caa ttg gtt gtc gtc aac ttc caa tgg 96 Ile Ser Phe Asn Asp Cys Ser Gln Leu Val Val Val Asn Phe Gln Trp 20 25 30 cag gcc act atg ctc ctc atc ttc aag ggt ctc gtc tcc ttt gca gaa 144 Gln Ala Thr Met Leu Leu Ile Phe Lys Gly Leu Val Ser Phe Ala Glu 35 40 45 ctt cca gaa cca cca ctg cac tgc cca aga acc ctc ttg aga tgc tct 192 Leu Pro Glu Pro Pro Leu His Cys Pro Arg Thr Leu Leu Arg Cys Ser 50 55 60 tgc aga ata aga gat tat cat ctt caa gaa cgc aac tat gga acc tgc 240 Cys Arg Ile Arg Asp Tyr His Leu Gln Glu Arg Asn Tyr Gly Thr Cys 65 70 75 80 acc tcc gca cat gac gct ggt tta tgg cag ata ccc cga cca ttg cca 288 Thr Ser Ala His Asp Ala Gly Leu Trp Gln Ile Pro Arg Pro Leu Pro 85 90 95 tac cgc ttc ctt agc tca ggc ttt gtt gag tac tct gca gat aac cca 336 Tyr Arg Phe Leu Ser Ser Gly Phe Val Glu Tyr Ser Ala Asp Asn Pro 100 105 110 ata aga cgg tat ttt gtg acc cca gcc ata agg agc ctt gcc ctc ctt 384 Ile Arg Arg Tyr Phe Val Thr Pro Ala Ile Arg Ser Leu Ala Leu Leu 115 120 125 gct gcc att ctc ctg gtg gcc ctg cag gct cgg gcg gag cca ctc cag 432 Ala Ala Ile Leu Leu Val Ala Leu Gln Ala Arg Ala Glu Pro Leu Gln 130 135 140 gca att gct gat gag gct aca gcc cag gag cag cct gga gca gat gat 480 Ala Ile Ala Asp Glu Ala Thr Ala Gln Glu Gln Pro Gly Ala Asp Asp 145 150 155 160 cag gaa gtg gtt gat tcc ttt gca tgg gat gaa aga gct cct ctt cag 528 Gln Glu Val Val Asp Ser Phe Ala Trp Asp Glu Arg Ala Pro Leu Gln 165 170 175 gtt tca ggg aag tcc tct cct gtt tgt gca cgg ctg ctc ttg cta cag 576 Val Ser Gly Lys Ser Ser Pro Val Cys Ala Arg Leu Leu Leu Leu Gln 180 185 190 gag acc cgg gac aga gga ctg ctg ttt gcc ctc cct ctt cac tct gcc 624 Glu Thr Arg Asp Arg Gly Leu Leu Phe Ala Leu Pro Leu His Ser Ala 195 200 205 tac ctt gag gat ctg ctc agg cag agc cac ttc agg caa gag ctg atg 672 Tyr Leu Glu Asp Leu Leu Arg Gln Ser His Phe Arg Gln Glu Leu Met 210 215 220 aag ctg cag ccc agg agc agc ctg gag cag atg atc agg aaa tgg ctc 720 Lys Leu Gln Pro Arg Ser Ser Leu Glu Gln Met Ile Arg Lys Trp Leu 225 230 235 240 atg cct tta cat ggc atg aaa gtg ccg ctc ttc cgc ttt cag cct gat 768 Met Pro Leu His Gly Met Lys Val Pro Leu Phe Arg Phe Gln Pro Asp 245 250 255 aaa atc att gtc ctc tcc acc ctg att cct aca gga gac tac tca ccc 816 Lys Ile Ile Val Leu Ser Thr Leu Ile Pro Thr Gly Asp Tyr Ser Pro 260 265 270 cat aac ctc aaa aac ctc ttc atg agg atg gtg acc cca gcc atg agg 864 His Asn Leu Lys Asn Leu Phe Met Arg Met Val Thr Pro Ala Met Arg 275 280 285 acc ctc gcc atc ctt gct gcc att ctc ctg gtg gcc ctg cag gcc cag 912 Thr Leu Ala Ile Leu Ala Ala Ile Leu Leu Val Ala Leu Gln Ala Gln 290 295 300 gct gag cca ctc cag gca aga gct gat gag gtt gct gca gcc ccg gag 960 Ala Glu Pro Leu Gln Ala Arg Ala Asp Glu Val Ala Ala Ala Pro Glu 305 310 315 320 cag att gca gcg gac atc cca gaa gtg gtt gtt tcc ctt gca tgg gac 1008 Gln Ile Ala Ala Asp Ile Pro Glu Val Val Val Ser Leu Ala Trp Asp 325 330 335 gaa agc ttg gct cca aag cat cca ggc tca agg aaa aac atg gac tgc 1056 Glu Ser Leu Ala Pro Lys His Pro Gly Ser Arg Lys Asn Met Asp Cys 340 345 350 tat tgc aga ata cca gcg tgc att gca gga gaa cgt cgc tat gga acc 1104 Tyr Cys Arg Ile Pro Ala Cys Ile Ala Gly Glu Arg Arg Tyr Gly Thr 355 360 365 tgc atc tac cag gga aga ctc tgg gca ttc tgc tgc tga gcttgcagaa 1153 Cys Ile Tyr Gln Gly Arg Leu Trp Ala Phe Cys Cys * 370 375 380 aaagaaaaat gagctcaaaa tttgctttga gagctacagg gaattgctat tactcctgta 1213 ccttctgctc aatttccttt cctcatctca aataaatggt cgacgcggcc gcgaattcgg 1273 atcctcgaga gatctctttt tttgggtttg gtggggtatc ttcatcatcg aatagatagt 1333 tatatacatc atgct 1348 79 645 DNA Homo sapiens CDS (132)..(362) misc_feature (1)...(645) n = a,t,c or g 79 cttggtatag gcagtaccca gctgnctann ntttgtatag cgagacccaa gctggctagc 60 gtttaaactt aagcttggta ccgagctcgg atccactagt ccagtgtggt ggaattcgcg 120 gagtatacac c atg agc aaa gct cac cct ccc gag ttg aaa aaa ttt atg 170 Met Ser Lys Ala His Pro Pro Glu Leu Lys Lys Phe Met 1 5 10 gac aag aag tta tca ttg aaa tta aat ggt ggc aga cat gtc caa gga 218 Asp Lys Lys Leu Ser Leu Lys Leu Asn Gly Gly Arg His Val Gln Gly 15 20 25 ata ttg cgg gga ttt gat ccc ttt atg aac ctt gtg ata gat gaa tgt 266 Ile Leu Arg Gly Phe Asp Pro Phe Met Asn Leu Val Ile Asp Glu Cys 30 35 40 45 gtg gag atg gcg act agt gga caa cag aac aat att gga atg gtg gta 314 Val Glu Met Ala Thr Ser Gly Gln Gln Asn Asn Ile Gly Met Val Val 50 55 60 ata cga gga aat agt atc atc atg tta gaa gcc ttg gaa cga gta taa 362 Ile Arg Gly Asn Ser Ile Ile Met Leu Glu Ala Leu Glu Arg Val * 65 70 75 ataatggctg ttcagcagag aaacccatgt cctctctcca tagggcctgt tttactatga 422 tgtaaaaatt aggtcatgta cattttcata ttagactttt tgttaaataa acttttgtaa 482 tagtcaaaaa tgctttttca gatgttttga atatagaaaa tcagctctca ttccagtttt 542 ttttaacatg aattttcctg gttgacattg atttcaaagg gttttatgca ttaaagtgaa 602 agaattttat taaatgtgaa acatggcaag gaaaaaaaaa aaa 645 80 2083 DNA Homo sapiens CDS (82)..(1821) 80 aattcccggg tcgacgattt cgtgcggccg ggagcccgcc gcgctggtag cgatattaat 60 aaggcagcgg aaagaagaaa t atg aat acg gct cca tca aga ccc agc ccc 111 Met Asn Thr Ala Pro Ser Arg Pro Ser Pro 1 5 10 aca cga agg gat cca tat ggc ttt gga gac agt cga gat tca agg cgt 159 Thr Arg Arg Asp Pro Tyr Gly Phe Gly Asp Ser Arg Asp Ser Arg Arg 15 20 25 gat cga tcc cca att cga gga agt cca agg aga gag ccc agg gat ggc 207 Asp Arg Ser Pro Ile Arg Gly Ser Pro Arg Arg Glu Pro Arg Asp Gly 30 35 40 aga aat ggc cgg gat gcc cgg gac agc aga gac att cga gac ccc cga 255 Arg Asn Gly Arg Asp Ala Arg Asp Ser Arg Asp Ile Arg Asp Pro Arg 45 50 55 gac ttg cgg gac cac aga cat agt aga gat ttg cgg gat cac aga gac 303 Asp Leu Arg Asp His Arg His Ser Arg Asp Leu Arg Asp His Arg Asp 60 65 70 agc agg agt gtg cgc gac gtt cgg gac gtg agg gat ctt aga gac ttt 351 Ser Arg Ser Val Arg Asp Val Arg Asp Val Arg Asp Leu Arg Asp Phe 75 80 85 90 cgt gat cta aga gac tct agg gat ttt cga gat cag cga gac ccc atg 399 Arg Asp Leu Arg Asp Ser Arg Asp Phe Arg Asp Gln Arg Asp Pro Met 95 100 105 tac gac aga tac aga gac atg aga gac tcc cga gat cct atg tac agg 447 Tyr Asp Arg Tyr Arg Asp Met Arg Asp Ser Arg Asp Pro Met Tyr Arg 110 115 120 aga gaa ggc tct tat gac cga tac cta cga atg gat gac tat tgc agg 495 Arg Glu Gly Ser Tyr Asp Arg Tyr Leu Arg Met Asp Asp Tyr Cys Arg 125 130 135 aga aag gat gac tct tat ttt gac cgt tac aga gat agc ttt gat gga 543 Arg Lys Asp Asp Ser Tyr Phe Asp Arg Tyr Arg Asp Ser Phe Asp Gly 140 145 150 cgg ggc cct cca ggc cca gaa agt cag tct cgt gca aaa gag cgt ttg 591 Arg Gly Pro Pro Gly Pro Glu Ser Gln Ser Arg Ala Lys Glu Arg Leu 155 160 165 170 aaa cgt gag gaa cgg cgt aga gaa gag ctt tat cgt caa tat ttt gag 639 Lys Arg Glu Glu Arg Arg Arg Glu Glu Leu Tyr Arg Gln Tyr Phe Glu 175 180 185 gaa atc cag aga cgc ttt gat gcc gaa agg ccc gtt gat tgt tct gtg 687 Glu Ile Gln Arg Arg Phe Asp Ala Glu Arg Pro Val Asp Cys Ser Val 190 195 200 att gtg gtc aac aaa cag aca aaa gac tat gct gag tct gtg ggg cgg 735 Ile Val Val Asn Lys Gln Thr Lys Asp Tyr Ala Glu Ser Val Gly Arg 205 210 215 aag gtg cga gac ctg ggc atg gta gtg gac ttg atc ttc ctt aac aca 783 Lys Val Arg Asp Leu Gly Met Val Val Asp Leu Ile Phe Leu Asn Thr 220 225 230 gaa gtg tca ctg tca caa gcc ttg gag gat gtt agc agg gga ggt tct 831 Glu Val Ser Leu Ser Gln Ala Leu Glu Asp Val Ser Arg Gly Gly Ser 235 240 245 250 cct ttt gct att gtc atc acc cag caa cac cag att cac cgc tcc tgc 879 Pro Phe Ala Ile Val Ile Thr Gln Gln His Gln Ile His Arg Ser Cys 255 260 265 aca gtc aac atc atg ttt gga acc ccg caa gag cat cgc aac atg ccc 927 Thr Val Asn Ile Met Phe Gly Thr Pro Gln Glu His Arg Asn Met Pro 270 275 280 caa gca gat gcc atg gtg ctg gtg gcc aga aat tat gag cgt tac aag 975 Gln Ala Asp Ala Met Val Leu Val Ala Arg Asn Tyr Glu Arg Tyr Lys 285 290 295 aat gag tgc cgg gag aag gaa cgt gag gag att gcc aga cag gca gcc 1023 Asn Glu Cys Arg Glu Lys Glu Arg Glu Glu Ile Ala Arg Gln Ala Ala 300 305 310 aag atg gcc gat gaa gcc atc ctg cag gaa aga gag aga gga ggc cct 1071 Lys Met Ala Asp Glu Ala Ile Leu Gln Glu Arg Glu Arg Gly Gly Pro 315 320 325 330 gag gag gga gtg cgt ggg ggc cac cct cca gcc atc cag agc ctc atc 1119 Glu Glu Gly Val Arg Gly Gly His Pro Pro Ala Ile Gln Ser Leu Ile 335 340 345 aac ctg ctg gca gac aac agg tac ctc act gct gaa gag act gac aag 1167 Asn Leu Leu Ala Asp Asn Arg Tyr Leu Thr Ala Glu Glu Thr Asp Lys 350 355 360 atc atc aac tac ctg cga gag cgg aag gag cgg ctg atg agg agc agc 1215 Ile Ile Asn Tyr Leu Arg Glu Arg Lys Glu Arg Leu Met Arg Ser Ser 365 370 375 acc gac tct ctg cct ggc ccg att tcc cgc caa cca ctc ggg gcg acc 1263 Thr Asp Ser Leu Pro Gly Pro Ile Ser Arg Gln Pro Leu Gly Ala Thr 380 385 390 tcg ggt gcc tcg ctg aag aca cag cca agc tcc caa ccg ctc cag agc 1311 Ser Gly Ala Ser Leu Lys Thr Gln Pro Ser Ser Gln Pro Leu Gln Ser 395 400 405 410 ggc caa gtg ctc ccc tct gct aca ccc act cca tct gca ccc ccc acc 1359 Gly Gln Val Leu Pro Ser Ala Thr Pro Thr Pro Ser Ala Pro Pro Thr 415 420 425 tcc cag caa gag ctt cag gcc aaa atc ctc agc ctc ttc aat agt ggc 1407 Ser Gln Gln Glu Leu Gln Ala Lys Ile Leu Ser Leu Phe Asn Ser Gly 430 435 440 aca gtg acg gcc aat agc agc tct gca tcc ccc tcg gtt gct gcc gga 1455 Thr Val Thr Ala Asn Ser Ser Ser Ala Ser Pro Ser Val Ala Ala Gly 445 450 455 aac acc cca aac cag aat ttt tcc aca gca gca aac agc cag cct caa 1503 Asn Thr Pro Asn Gln Asn Phe Ser Thr Ala Ala Asn Ser Gln Pro Gln 460 465 470 caa aga tca cag gct tct ggc aat cag cct cca agc att ttg gga cag 1551 Gln Arg Ser Gln Ala Ser Gly Asn Gln Pro Pro Ser Ile Leu Gly Gln 475 480 485 490 gga gga tct gct cag aac atg ggc ccc aga cct ggg gct cct tcc caa 1599 Gly Gly Ser Ala Gln Asn Met Gly Pro Arg Pro Gly Ala Pro Ser Gln 495 500 505 ggg ctt ttt ggc cag cct tcc agt cgc ctg gca cct gct agc aac atg 1647 Gly Leu Phe Gly Gln Pro Ser Ser Arg Leu Ala Pro Ala Ser Asn Met 510 515 520 act agc cag agg cct gtg tct tcc aca ggt atc aac ttt gac aat cca 1695 Thr Ser Gln Arg Pro Val Ser Ser Thr Gly Ile Asn Phe Asp Asn Pro 525 530 535 agt gta cag aag gct ctg gat acc ctg atc cag agt ggc cct gct ctc 1743 Ser Val Gln Lys Ala Leu Asp Thr Leu Ile Gln Ser Gly Pro Ala Leu 540 545 550 tcc cac ctg gtt agc cag acc aca gca cag atg ggg cag cca cag gcc 1791 Ser His Leu Val Ser Gln Thr Thr Ala Gln Met Gly Gln Pro Gln Ala 555 560 565 570 ccc atg gga tct tac cag agg cat tac tga a gctaaatctt tcaactctcc 1842 Pro Met Gly Ser Tyr Gln Arg His Tyr * 575 580 ccagtcccct catcccctgg cctcctccca cttacttgtt ctaaatagag ctgtttggag 1902 gatgttctct gcgctcccag gccggcatcg agtgtcatca atttctacca cctgctctct 1962 cttctgccca aggctgtgtt gcttattcct tacaaagttt atactgcatt tggggctgta 2022 tctttttttg ttttttgttt tgtagaaaat aaatatctcc gggggcagta aaaaaaaaaa 2082 a 2083 81 471 DNA Homo sapiens CDS (186)..(341) 81 ccctgttctt ctttacctaa ctctatagca gtaattggta catttcttcc atcaaagttt 60 catattttta gcaaagtatc aagccttacc gtacggaaag ctgcaaccac aagattggag 120 ggaaacaggt ttctgttgga aaagaaagca ttctgtcagt attcttttaa aacaattttt 180 tagag atg agg tcc ctg ttg ccc agg ctg gag tgc agt ggt gtg att 227 Met Arg Ser Leu Leu Pro Arg Leu Glu Cys Ser Gly Val Ile 1 5 10 gca gct cac tgc agc ctt gaa ctt ttg ggc tca agt gat cct cct gcc 275 Ala Ala His Cys Ser Leu Glu Leu Leu Gly Ser Ser Asp Pro Pro Ala 15 20 25 30 tca gcc tcc caa agt gtt ggg act aca ggc gtg agc cat ggt acc tgt 323 Ser Ala Ser Gln Ser Val Gly Thr Thr Gly Val Ser His Gly Thr Cys 35 40 45 ctt cat cag tat tct taa aattca gtgtgcaaag tatctgcttt gagatgtcca 377 Leu His Gln Tyr Ser * 50 cttctaaaac cctaacacag tgttctctct ccacccctag ctgacactgc accttttgct 437 tctcgtgccg aattcttggc ctcgagggcc aaat 471 82 2693 DNA Homo sapiens CDS (79)..(2337) 82 gacagatctg cgcgtatcct ggagccggcc cagttgtgaa ctaggagagc tttgggacct 60 ctgtcccaag caagagag atg aat gga gag tat aga ggc aga gga ttt gga 111 Met Asn Gly Glu Tyr Arg Gly Arg Gly Phe Gly 1 5 10 cga gga aga ttt caa agc tgg aaa agg gga aga ggt ggt ggg aac ttc 159 Arg Gly Arg Phe Gln Ser Trp Lys Arg Gly Arg Gly Gly Gly Asn Phe 15 20 25 tca gga aaa tgg aga gaa aga gaa cac aga cct gat ctg agt aaa acc 207 Ser Gly Lys Trp Arg Glu Arg Glu His Arg Pro Asp Leu Ser Lys Thr 30 35 40 aca gga aaa cgt act tct ggg gac tta ata caa gaa att gga tac aaa 255 Thr Gly Lys Arg Thr Ser Gly Asp Leu Ile Gln Glu Ile Gly Tyr Lys 45 50 55 aat gga aga ctg aaa gag cag aaa gga aat att gag gta act ccc cag 303 Asn Gly Arg Leu Lys Glu Gln Lys Gly Asn Ile Glu Val Thr Pro Gln 60 65 70 75 aaa gta gta att cag gaa gca gca acc atc ctt atg gct aag aga cta 351 Lys Val Val Ile Gln Glu Ala Ala Thr Ile Leu Met Ala Lys Arg Leu 80 85 90 aaa gaa gtt ctg agg tta cca gaa tgt ggg aat tca aag gat gaa ata 399 Lys Glu Val Leu Arg Leu Pro Glu Cys Gly Asn Ser Lys Asp Glu Ile 95 100 105 gaa aga aag gga agt att ttg gta gat ttt aaa gaa ctg aca gaa ggt 447 Glu Arg Lys Gly Ser Ile Leu Val Asp Phe Lys Glu Leu Thr Glu Gly 110 115 120 ggt gaa gta act aac ttg ata cca gat ata gca act gaa cta aga gat 495 Gly Glu Val Thr Asn Leu Ile Pro Asp Ile Ala Thr Glu Leu Arg Asp 125 130 135 gca cct gag aaa acc ttg gct tgc atg ggt ttg gca ata cat cag gtg 543 Ala Pro Glu Lys Thr Leu Ala Cys Met Gly Leu Ala Ile His Gln Val 140 145 150 155 tta act aag gac ctt gaa agg cat gca gct gag tta caa gcc cag gaa 591 Leu Thr Lys Asp Leu Glu Arg His Ala Ala Glu Leu Gln Ala Gln Glu 160 165 170 gga ttg tct aat gat gga gaa aca atg gta aat gtg cca cat att cat 639 Gly Leu Ser Asn Asp Gly Glu Thr Met Val Asn Val Pro His Ile His 175 180 185 gca agg gtg tac aac tat gag cct ttg aca cag ctc aag aat gtc aga 687 Ala Arg Val Tyr Asn Tyr Glu Pro Leu Thr Gln Leu Lys Asn Val Arg 190 195 200 gca aat tac tat gga aaa tac att gct cta aga ggg aca gtg gtt cgt 735 Ala Asn Tyr Tyr Gly Lys Tyr Ile Ala Leu Arg Gly Thr Val Val Arg 205 210 215 gtc agt aat ata aag cct ctt tgc acc aag atg gct ttt ctt tgt gct 783 Val Ser Asn Ile Lys Pro Leu Cys Thr Lys Met Ala Phe Leu Cys Ala 220 225 230 235 gca tgt gga gaa att cag agc ttt cct ctt cca gat gga aaa tac agt 831 Ala Cys Gly Glu Ile Gln Ser Phe Pro Leu Pro Asp Gly Lys Tyr Ser 240 245 250 ctt ccc aca aag tgt cct gtg cct gtg tgt cga ggc agg tca ttt act 879 Leu Pro Thr Lys Cys Pro Val Pro Val Cys Arg Gly Arg Ser Phe Thr 255 260 265 gct ctc cgc agc tct cct ctc aca gtt acg atg gac tgg cag tca atc 927 Ala Leu Arg Ser Ser Pro Leu Thr Val Thr Met Asp Trp Gln Ser Ile 270 275 280 aaa atc cag gaa ttg atg tct gat gat cag aga gaa gca ggt cgg att 975 Lys Ile Gln Glu Leu Met Ser Asp Asp Gln Arg Glu Ala Gly Arg Ile 285 290 295 cca cga aca ata gaa tgt gag ctt gtt cat gat ctt gtg gat agc tgt 1023 Pro Arg Thr Ile Glu Cys Glu Leu Val His Asp Leu Val Asp Ser Cys 300 305 310 315 gtc ccg gga gac aca gtg act att act gga att gtc aaa gtc tca aat 1071 Val Pro Gly Asp Thr Val Thr Ile Thr Gly Ile Val Lys Val Ser Asn 320 325 330 gcg gaa gaa ggt ttg gca tta gca ctc ttt gga gga agc cag aaa tac 1119 Ala Glu Glu Gly Leu Ala Leu Ala Leu Phe Gly Gly Ser Gln Lys Tyr 335 340 345 gca gat gac aaa aac aga att cca att cgg gga gac ccc cac atc ctt 1167 Ala Asp Asp Lys Asn Arg Ile Pro Ile Arg Gly Asp Pro His Ile Leu 350 355 360 gtt gtt gga gat cca ggc cta gga aaa agt caa atg cta cag gca gcg 1215 Val Val Gly Asp Pro Gly Leu Gly Lys Ser Gln Met Leu Gln Ala Ala 365 370 375 tgc aat gtt gcc cca cgt ggc gtg tat gtt tgt ggt aac acc acg acc 1263 Cys Asn Val Ala Pro Arg Gly Val Tyr Val Cys Gly Asn Thr Thr Thr 380 385 390 395 acc tct ggt ctg acg gta act ctt tca aaa gat agt tcc tct gga gat 1311 Thr Ser Gly Leu Thr Val Thr Leu Ser Lys Asp Ser Ser Ser Gly Asp 400 405 410 ttt gct ttg gaa gct ggt gcc ctg gta ctt ggt gat caa ggt att tgt 1359 Phe Ala Leu Glu Ala Gly Ala Leu Val Leu Gly Asp Gln Gly Ile Cys 415 420 425 gga atc gat gaa ttt gat aag atg ggg aat caa cat caa gcc ttg ttg 1407 Gly Ile Asp Glu Phe Asp Lys Met Gly Asn Gln His Gln Ala Leu Leu 430 435 440 gaa gcc atg gag cag caa agt att agt ctt gct aag gct ggt gtg gtt 1455 Glu Ala Met Glu Gln Gln Ser Ile Ser Leu Ala Lys Ala Gly Val Val 445 450 455 tgt agc ctt cct gca aga act tcc att att gct gct gca aat cca gtt 1503 Cys Ser Leu Pro Ala Arg Thr Ser Ile Ile Ala Ala Ala Asn Pro Val 460 465 470 475 gga gga cat tac aat aaa gcc aaa aca gtt tct gag aat tta aaa atg 1551 Gly Gly His Tyr Asn Lys Ala Lys Thr Val Ser Glu Asn Leu Lys Met 480 485 490 ggg agt gca cta cta tcc aga ttt gat ttg gtc ttt atc ctg tta gat 1599 Gly Ser Ala Leu Leu Ser Arg Phe Asp Leu Val Phe Ile Leu Leu Asp 495 500 505 act cca aat gag cat cat gat cac tta ctc tct gaa cat gtg att gca 1647 Thr Pro Asn Glu His His Asp His Leu Leu Ser Glu His Val Ile Ala 510 515 520 ata aga gct gga aag cag aga acc att agc agt gcc aca gta gct cgt 1695 Ile Arg Ala Gly Lys Gln Arg Thr Ile Ser Ser Ala Thr Val Ala Arg 525 530 535 atg aat agt caa gat tca aat act tcc gta ctt gaa gta gtt tct gag 1743 Met Asn Ser Gln Asp Ser Asn Thr Ser Val Leu Glu Val Val Ser Glu 540 545 550 555 aag cca tta tca gaa aga cta aag gtg gtt cct gga gaa aca ata gat 1791 Lys Pro Leu Ser Glu Arg Leu Lys Val Val Pro Gly Glu Thr Ile Asp 560 565 570 ccc att ccc cac cag cta ttg aga aag tac att ggc tat gct cgg cag 1839 Pro Ile Pro His Gln Leu Leu Arg Lys Tyr Ile Gly Tyr Ala Arg Gln 575 580 585 tat gtg tac cca agg cta tcc aca gaa gct gct cga gtt ctt caa gat 1887 Tyr Val Tyr Pro Arg Leu Ser Thr Glu Ala Ala Arg Val Leu Gln Asp 590 595 600 ttt tac ctt gag ctc cgg aaa cag agc cag agg tta aat agc tca cca 1935 Phe Tyr Leu Glu Leu Arg Lys Gln Ser Gln Arg Leu Asn Ser Ser Pro 605 610 615 atc act acc agg cag ctg gaa tct ttg att cgt ctg aca gag gca cga 1983 Ile Thr Thr Arg Gln Leu Glu Ser Leu Ile Arg Leu Thr Glu Ala Arg 620 625 630 635 gca agg ttg gaa ttg aga gag gaa gca acc aaa gaa gac gct gag gat 2031 Ala Arg Leu Glu Leu Arg Glu Glu Ala Thr Lys Glu Asp Ala Glu Asp 640 645 650 ata gtg gaa att atg aaa tat agc atg cta gga act tac tct gat gaa 2079 Ile Val Glu Ile Met Lys Tyr Ser Met Leu Gly Thr Tyr Ser Asp Glu 655 660 665 ttt ggg aac cta gat ttt gag cga tcc cag cat ggt tct gga atg agc 2127 Phe Gly Asn Leu Asp Phe Glu Arg Ser Gln His Gly Ser Gly Met Ser 670 675 680 aac agg tca aca gcg aaa aga ttt att tct gct ctc aac aac gtt gct 2175 Asn Arg Ser Thr Ala Lys Arg Phe Ile Ser Ala Leu Asn Asn Val Ala 685 690 695 gaa aga act tat aat aat ata ttt caa ttt cat caa ctt cgg cag att 2223 Glu Arg Thr Tyr Asn Asn Ile Phe Gln Phe His Gln Leu Arg Gln Ile 700 705 710 715 gcc aaa gaa cta aac att cag gtt gct gat ttt gaa aat ttt att gga 2271 Ala Lys Glu Leu Asn Ile Gln Val Ala Asp Phe Glu Asn Phe Ile Gly 720 725 730 tca cta aat gac cag ggt tac ctc ttg aaa aaa ggc cca aaa gtt tac 2319 Ser Leu Asn Asp Gln Gly Tyr Leu Leu Lys Lys Gly Pro Lys Val Tyr 735 740 745 cag ctt caa act atg taa aaggac ttcaccaagt tagggcctcc tgggtttatt 2373 Gln Leu Gln Thr Met * 750 gcagattaaa gccatctcag tgaagatatg cgtgcacgca cagacagaca gacacacaca 2433 cacacacaca cacacacaca cacacacaca cacacagtca aatactgttc tctgaaaaat 2493 gatgtcccaa aagtattata ataggaaaaa agcattaaat ataataaact aatttaagaa 2553 gtgataaagt ctccagatgc agtagctcac actgtaatca cagtgactca ggaggctgag 2613 gtgagaggat tccttgaggc cagggttcga gaccaacctt gggcaacata gcaagacccc 2673 atttcttaaa aaaaaaaaaa 2693 83 1141 DNA Homo sapiens CDS (556)..(867) 83 taagcttgcg gccgcccttt tgagtacctc tgtccaggac tgaagacgaa ccttggccgc 60 agtccttgcg aactgttcgc aaaacagtgc gggctgcggt gggtcagcgt cacatgctaa 120 tgacaggatg ttcctcgtag ctttttattt tgtgcgtctt atgtttgtat agtgtgttgt 180 cattttgatt tttttttttt tttaagtata aaagctgctt agaatagttc tatcatgaag 240 ggcacttttc agattgtggg ctggaaaggg ttattttatc tgtgggggag ggagggagac 300 gtgaagccta tttaaaatga gcctgtgacg attatgcaca tgaccagagg cggccggtaa 360 tcagggcaga gtctggtgtg gaccgccggg cgcagagcgg ctccgcggcg ggagctgagc 420 ggaaggcgcg ggctgcgatc tgctctctgt tcccctggat ccgcctatgc acattaccct 480 tgtttcatta ctttttcatg tcattttttt atcccaaaaa atatttttta aaagttaaaa 540 aaagacatat caaac atg caa ata ctt gaa tcc agc agg cca ata gtg aaa 591 Met Gln Ile Leu Glu Ser Ser Arg Pro Ile Val Lys 1 5 10 tgt gaa cac ttt cta att cta cac ttc cag gtt gac atc agt aca cag 639 Cys Glu His Phe Leu Ile Leu His Phe Gln Val Asp Ile Ser Thr Gln 15 20 25 aaa cag gct cta gga aaa att tct aag ttc ata gcc tac gtg tgt gta 687 Lys Gln Ala Leu Gly Lys Ile Ser Lys Phe Ile Ala Tyr Val Cys Val 30 35 40 tgt gtg cgt gtt gaa aca gaa gtg tgt gtg tgt gtg cat gtg tgg cgc 735 Cys Val Arg Val Glu Thr Glu Val Cys Val Cys Val His Val Trp Arg 45 50 55 60 gtg ctc ctg cac ggc gtg cag ttt tct gtg ttt gtg tgt ttg aaa gcg 783 Val Leu Leu His Gly Val Gln Phe Ser Val Phe Val Cys Leu Lys Ala 65 70 75 tgt gag gat tta act gtg ggt ttt ccc ttg tat tca gta tac gct ttt 831 Cys Glu Asp Leu Thr Val Gly Phe Pro Leu Tyr Ser Val Tyr Ala Phe 80 85 90 ttt ttg gcg cat tgg tca aac ggt tgt tat tat tag cttc taactttgca 881 Phe Leu Ala His Trp Ser Asn Gly Cys Tyr Tyr * 95 100 ctgagtgtcc tcgcccttcc tttagctaat cctatacatt acagagaatt cctaggacag 941 ggctggcgac aattcatgtg taaatgttta ctcaaggact ctgtgactgc gtttaaaaag 1001 tacagtgtat atctctggag aaataacatg tatacctacc tttagcagct ttttattgtg 1061 gactaatgca agaaaattat taccagagta ttgcaccatt tttccatttg gaatataaag 1121 ttaaagagaa aaaaaaaaaa 1141 84 2232 DNA Homo sapiens CDS (1298)..(2017) 84 atttggccct cgaggccaag aattcggcac gagcgacctg gcatggtttt aagtgatatt 60 aagagtattg gcttatattt aagaagtcaa aagataccac tttatgagga atgccagctt 120 ttggtgagaa aaggatttga ttttcagaga aaacagtatg gcaaactaaa gaagtttact 180 actgtaaatc ctgagtttta taatgaacca aaaaccaaac tttatcttaa gctaagtcgg 240 aaggaaagat cttcagctta tagcaaaaat gatctttggg tggtttcaaa aaccctagac 300 tttgagctgg atacttttat cgcatgtagt gctttctttg gaccatcatc tatcaatgag 360 atagaaatac tgcctttgaa aggctatttc ccttctaatt ggcccactaa catggttgtc 420 catgcgttat tggtttgtaa tgctagcaca gaactgacta ctttgaaaaa cattcaggac 480 tactttaatc cagctactct acctctaaca cagtacctgt taacaacgtc ttcgccaact 540 atagttagta acaaaagagt cagtaagaga aaatttatcc caccagcctt cacaaatgtc 600 agtacaaaat ttgaactact cagcctagga gcaacattga agttagctag tgagttgatt 660 caggtacaca agttaaacaa ggatcaagct acagctctaa ttcaaatagc tcaaatgatg 720 gcatcacatg aaagcattga agaagtgaag gaactgcaaa ctcatacctt ccctatcaca 780 atcatacatg gtgtgtttgg agcaggaaag agttacttgc tggcagtggt gattttgttc 840 tttgtacagc tgtttgaaaa gagtgaagct cccaccattg gaaatgcaag gccgtggaaa 900 cttctgattt cttcttctac taatgtggct gttgacagag tacttcttgg gcttctcagt 960 cttggatttg aaaactttat cagagttggg agtgttagga agattgccaa accaatttta 1020 ccttatagct tgcatgctgg ctcaaaaaat gaaagtgaac agttaaaaga actacatgca 1080 ctaatgaaag aagacctgac tcctacggaa agagtctatg tgagaaaaag cattgagcag 1140 cataaactgg ggaccaatag aaccctgctg aagcaggttc gagtgtgaaa agctgattct 1200 tgttggggat cccaaacagc tacctcctac tattcagggt tctgatgcag ctcatgaaaa 1260 tggattggaa caaactcttt ttgatcgact ttgctta atg ggt cac aag cca att 1315 Met Gly His Lys Pro Ile 1 5 cta ttg aga act caa tac cgt tgt cat cct gca atc agt gct att gct 1363 Leu Leu Arg Thr Gln Tyr Arg Cys His Pro Ala Ile Ser Ala Ile Ala 10 15 20 aat gat ctg ttt tac aaa gga gcc ctc atg aat ggt gta aca gaa ata 1411 Asn Asp Leu Phe Tyr Lys Gly Ala Leu Met Asn Gly Val Thr Glu Ile 25 30 35 gag cgg agc cct tta ttg gaa tgg cta cca acc ctg tgt ttt tat aat 1459 Glu Arg Ser Pro Leu Leu Glu Trp Leu Pro Thr Leu Cys Phe Tyr Asn 40 45 50 gtt aaa gga cta gaa cag ata gaa aga gat aac agc ttt cat aat gtg 1507 Val Lys Gly Leu Glu Gln Ile Glu Arg Asp Asn Ser Phe His Asn Val 55 60 65 70 gca gaa gct acg ttt aca ctc aag ctg att caa tca ctg att gca agt 1555 Ala Glu Ala Thr Phe Thr Leu Lys Leu Ile Gln Ser Leu Ile Ala Ser 75 80 85 gga ata gca ggc tct atg att ggt gtg ata aca tta tac aaa tcc cag 1603 Gly Ile Ala Gly Ser Met Ile Gly Val Ile Thr Leu Tyr Lys Ser Gln 90 95 100 atg tac aag ctt tgt cat tta ctc agt gct gtg gac ttt cac cat cct 1651 Met Tyr Lys Leu Cys His Leu Leu Ser Ala Val Asp Phe His His Pro 105 110 115 gat att aaa act gtg cag gtg tcc aca gta gat gct ttt cag gga gct 1699 Asp Ile Lys Thr Val Gln Val Ser Thr Val Asp Ala Phe Gln Gly Ala 120 125 130 gaa aag gag atc att att ctg tcc tgt gta agg aca aga caa gta gga 1747 Glu Lys Glu Ile Ile Ile Leu Ser Cys Val Arg Thr Arg Gln Val Gly 135 140 145 150 ttc att gat tca gaa aaa aga atg aat gtt gca ttg act aga gga aag 1795 Phe Ile Asp Ser Glu Lys Arg Met Asn Val Ala Leu Thr Arg Gly Lys 155 160 165 agg cat ttg ttg att gtg gga aat tta gcc tgt ttg agg aaa aat caa 1843 Arg His Leu Leu Ile Val Gly Asn Leu Ala Cys Leu Arg Lys Asn Gln 170 175 180 ctt tgg gga cga gtg atc caa cac tgc gaa gga agg gaa gat gga ttg 1891 Leu Trp Gly Arg Val Ile Gln His Cys Glu Gly Arg Glu Asp Gly Leu 185 190 195 caa cat gca aac cag tat gaa cca cag ctg aac cat ctc ctt aaa gat 1939 Gln His Ala Asn Gln Tyr Glu Pro Gln Leu Asn His Leu Leu Lys Asp 200 205 210 tat ttt gaa aaa caa gtg gaa gaa aaa cag aag aaa aag agt gaa aaa 1987 Tyr Phe Glu Lys Gln Val Glu Glu Lys Gln Lys Lys Lys Ser Glu Lys 215 220 225 230 gag aaa tct aaa gat aaa tct cat tca taa a aagacatggt gtaaatattt 2038 Glu Lys Ser Lys Asp Lys Ser His Ser * 235 240 tgtatttatg taaattcaga ctcattttac atgatatatt ttttatattt ttattactct 2098 aaaccctctt attaaaaata tgatatttaa ataacatagt aaacacatgt aaaaattttg 2158 ttcttcaaaa aagtgtacaa aaggtagtat aaaatcctac taataaaaat aagctttttt 2218 ctaaaaaaaa aaaa 2232 85 1308 DNA Homo sapiens CDS (277)..(777) 85 atttggccct cgaggccaag aattcggcac gaggcgatta gcgccaacag ctcagagaaa 60 acgtgacgaa aaccagtctg taaaacccga gcctgggaga ggggcttcgg tgcgcggggg 120 gaatttgcag acgctccctg ctggcggaga tttcctgacc tgtccttcgg cgcgggactt 180 tcggcgggtc ccggccgggc agacccaagt gccggcggcg gagactgcag tggagccagt 240 accggctgta gtggccgggg ccgtggcggg agagtc atg tca gag ccg cag ccg 294 Met Ser Glu Pro Gln Pro 1 5 cgg ggc gca gag cgc gat ctc tac cgg gac acg tgg gtg cga tac ctg 342 Arg Gly Ala Glu Arg Asp Leu Tyr Arg Asp Thr Trp Val Arg Tyr Leu 10 15 20 ggc tat gcc aat gag gtg ggc gag gct ttc cgc tct ctt gtg cca gcg 390 Gly Tyr Ala Asn Glu Val Gly Glu Ala Phe Arg Ser Leu Val Pro Ala 25 30 35 gcg gtg gtg tgg ctg agc tat ggc gtg gcc agc tcc tac gtg ctg gcg 438 Ala Val Val Trp Leu Ser Tyr Gly Val Ala Ser Ser Tyr Val Leu Ala 40 45 50 gat gcc att gac aaa ggc aag aag gct gga gag gtg ccc agc cct gaa 486 Asp Ala Ile Asp Lys Gly Lys Lys Ala Gly Glu Val Pro Ser Pro Glu 55 60 65 70 gca ggc cgc agc gcc agg gtg acc gtg gct gtg gtg gac acc ttt gta 534 Ala Gly Arg Ser Ala Arg Val Thr Val Ala Val Val Asp Thr Phe Val 75 80 85 tgg cag gct cta gcc tct gtg gcc att ccg ggc ttc acc atc aac cgc 582 Trp Gln Ala Leu Ala Ser Val Ala Ile Pro Gly Phe Thr Ile Asn Arg 90 95 100 gtg tgt gct gcc tct ctc tat gtc ctg ggc act gcc acc cgc tgg ccc 630 Val Cys Ala Ala Ser Leu Tyr Val Leu Gly Thr Ala Thr Arg Trp Pro 105 110 115 ctg gct gtc cgc aag tgg acc acc acc gcg ctt ggg ctg ttg acc atc 678 Leu Ala Val Arg Lys Trp Thr Thr Thr Ala Leu Gly Leu Leu Thr Ile 120 125 130 ccc atc att atc cac ccc att gac agg tcg gtg gat ttc ctc ctg gac 726 Pro Ile Ile Ile His Pro Ile Asp Arg Ser Val Asp Phe Leu Leu Asp 135 140 145 150 tcc agc ctg cgc aag ctc tac cca aca gtg ggg aag ccc agc tcc tcc 774 Ser Ser Leu Arg Lys Leu Tyr Pro Thr Val Gly Lys Pro Ser Ser Ser 155 160 165 tga tcat actctggtac ctggcctgtg catcggcctc ctgcttcatg tcaacctcct 831 * actcctgcca gggaatgtgg acacctggct ccctggtgtc caaagaccct ggcacctggg 891 tgggtttgag ctggacagaa gcttagagac aaaggcttca agaagcagtg gctgcaggga 951 gtcacagaag ggcaggacct gaacgctgtc tgcttccctg gaatccaaga tgctgagtgg 1011 aagtggaccc tgggtgggcc cggccctgtc tttttcagga aaattacatc ctcccatgga 1071 ggatgagaga ctgaggctca gggagggcaa ggaataggcc caagatcact tggcaagctg 1131 ggcacccagg acccccaggt gcttgacaga gtcaccccat ggtggtatgg ctgaacaagg 1191 agcggcagac aactcaggga gaaactcagg agtgcagtac cagggacacc tcaggacaga 1251 ttctctggcc aggcccttcc ctgacccaat aaatcctgaa gaggtaaaaa aaaaaaa 1308 86 1922 DNA Homo sapiens CDS (94)..(1116) 86 ttcctggatg tccttgaccg gaattcccgg gtcgacccac gcgtccgccc acgcgtccgg 60 gaacttggag cagccagaag aagtcagtat tac atg aaa tat ggg aat cca aat 114 Met Lys Tyr Gly Asn Pro Asn 1 5 tat gga ggc atg aaa gga att ctt agc aat tca tgg aag cga aga tat 162 Tyr Gly Gly Met Lys Gly Ile Leu Ser Asn Ser Trp Lys Arg Arg Tyr 10 15 20 cat tcc cgt cgt att cag cgg gac gtg atc aag aag aga gcc ctg att 210 His Ser Arg Arg Ile Gln Arg Asp Val Ile Lys Lys Arg Ala Leu Ile 25 30 35 ggg gat gac gtt ggc ttg acg tcg tat aaa cat cga cat tct ggg cta 258 Gly Asp Asp Val Gly Leu Thr Ser Tyr Lys His Arg His Ser Gly Leu 40 45 50 55 gtg aat gtt ccc gag gaa ccc att gaa gag gag gaa gag gag gag gag 306 Val Asn Val Pro Glu Glu Pro Ile Glu Glu Glu Glu Glu Glu Glu Glu 60 65 70 gag gaa gag gaa gag gaa gaa gaa gac cag gac atg gat gca gat gac 354 Glu Glu Glu Glu Glu Glu Glu Glu Asp Gln Asp Met Asp Ala Asp Asp 75 80 85 aga gtg gtg gta gag tac cac gag gag ctc ccg gct ctc aag cag ccc 402 Arg Val Val Val Glu Tyr His Glu Glu Leu Pro Ala Leu Lys Gln Pro 90 95 100 cgg gag cgg agc gcg tct aga cga tcc agt gcc agc agc tca gac tca 450 Arg Glu Arg Ser Ala Ser Arg Arg Ser Ser Ala Ser Ser Ser Asp Ser 105 110 115 gat gaa atg gac tat gat cta gaa ctg aaa atg att tcc acg cct tca 498 Asp Glu Met Asp Tyr Asp Leu Glu Leu Lys Met Ile Ser Thr Pro Ser 120 125 130 135 cca aag aaa agc atg aaa atg act atg tat gct gac gaa gtg gaa tct 546 Pro Lys Lys Ser Met Lys Met Thr Met Tyr Ala Asp Glu Val Glu Ser 140 145 150 cag ttg aaa aat att agg aac tcc atg agg gca gat agt gta tct tca 594 Gln Leu Lys Asn Ile Arg Asn Ser Met Arg Ala Asp Ser Val Ser Ser 155 160 165 agc aat atc aaa aac cga att ggt aac aaa tta cca cct gag aaa ttt 642 Ser Asn Ile Lys Asn Arg Ile Gly Asn Lys Leu Pro Pro Glu Lys Phe 170 175 180 gca gat gtc cga cat cta tta gat gag aaa cgt cag cac tcc cgt cca 690 Ala Asp Val Arg His Leu Leu Asp Glu Lys Arg Gln His Ser Arg Pro 185 190 195 cgg cca cca gtc agc agt act aaa tca gat ata cgc cag cgg tta gga 738 Arg Pro Pro Val Ser Ser Thr Lys Ser Asp Ile Arg Gln Arg Leu Gly 200 205 210 215 aaa aga cca cat tct ccg gaa aag gct ttt agt agt aac ccc gtc gtt 786 Lys Arg Pro His Ser Pro Glu Lys Ala Phe Ser Ser Asn Pro Val Val 220 225 230 cgg aga gag ccc tct tct gat gtg cat agt agg cta ggt gtt ccc agg 834 Arg Arg Glu Pro Ser Ser Asp Val His Ser Arg Leu Gly Val Pro Arg 235 240 245 cag gat agt aaa ggc ctc tac gcc gat act cgg gag aag aaa tca ggt 882 Gln Asp Ser Lys Gly Leu Tyr Ala Asp Thr Arg Glu Lys Lys Ser Gly 250 255 260 aat tta tgg act cgc cta gga tct gca ccc aag acc aaa gaa aag aat 930 Asn Leu Trp Thr Arg Leu Gly Ser Ala Pro Lys Thr Lys Glu Lys Asn 265 270 275 acg aag aaa gtg gat cac agg gcg cct ggc gct gag gaa gac gac tct 978 Thr Lys Lys Val Asp His Arg Ala Pro Gly Ala Glu Glu Asp Asp Ser 280 285 290 295 gag ctg caa agg gca tgg ggg gct ctg att aag gag aaa gag cag tct 1026 Glu Leu Gln Arg Ala Trp Gly Ala Leu Ile Lys Glu Lys Glu Gln Ser 300 305 310 cgc caa aag aag agc cgg tta gat aac tta cca tct ctc cag att gaa 1074 Arg Gln Lys Lys Ser Arg Leu Asp Asn Leu Pro Ser Leu Gln Ile Glu 315 320 325 gtt agt cgg gaa agc agc tct ggt tca gag gca gag tcc tga tgcccct 1123 Val Ser Arg Glu Ser Ser Ser Gly Ser Glu Ala Glu Ser * 330 335 340 ggggcctatg gcagctgccc taaagcctga cattcttgca cagggtgggg cgcgcagtag 1183 gaacctcccc cgcaggagct ggcgccctct cgctcctgct cacacagtca ccctccgctc 1243 ttgctacttc ggcaagacat cttaagaatg tgacacattt tcaagggcat ctctatcttt 1303 cgctgcagag ttgtagttct gggccctcga ttcctttccc accaccccac aggctttacc 1363 ctttgagaaa aaggcagccc tccagatttt gtagacattt ttcttaatat ttttaacatt 1423 gtgtctttta aaagaaatgt tttacacagt tcatccaaag agcagagaac tgaacttctc 1483 actattgcct tggccctgac agctgttacc agcacccttt tcccaagaaa agtcaattcc 1543 caggtgctta ttggacatcc ttcgaggggg aagaggaggg aagcggccag ctcacccttc 1603 cgggacccta gtgtggggcg aatctcacgg acctgacctc agaggtgcac cagtgccgcc 1663 caggtagata agagctgcag cattgactgt gcttccgttc ttccctcggg gattgctcat 1723 ggcatgggcc tcttacgtgc tgtcagcttg atgtgaagat caagttcagt gctgtgggat 1783 ttttaggaac aaaaaactgt gacgtctgga tttggggttg atttttgtgc tggggtggga 1843 ttatgggtca atgttgaaga atttttaagt ctgtattatg tttaaaacat gaatgatttg 1903 aaagtttaaa aaaaaaaaa 1922 87 1819 DNA Homo sapiens CDS (984)..(1409) 87 gcacgagccc ttcctcaccc cgtcccctga gtcccctgac cagtggtcca gctcgtcccc 60 gcattccaac gtctccgact ggtccgaggg cgtctccagc cctcccacca gcatgcagtc 120 ccagatcgcc cgcattccgg aggccttcaa gtaaacggcg cgccccacga gaccccggct 180 tcctttccca agccttcggg cgtctgtgtg cgctctgtgg atgccagggc cgaccagagg 240 agccttttta aaacacatgt ttttatacaa aataagaaca aggattttaa ttttttttag 300 tatttattta tgtactttta ttttacacag aaacactgcc tttttattta tatgtactgt 360 tttatctggc cccaggtaga aacttttatc tattctgaga aaacaagcaa gttctgagag 420 ccagggtttt cctacgtagg atgaaaagat tcttctgtgt ttataaaata taaacaaaga 480 ttcatgattt ataaatgcca tttatttatt gattcctttt ttcaaaatcc aaaaagaaat 540 gatgttggag aagggaagtt gaacgagcat agtccaaaaa gctcctgggg cgtccaggcc 600 gcgccctttc cccgacgccc acccaacccc aagccagccc ggccgctcca ccagcatcac 660 ctgcctgtta ggagaagctg catccagagg caaacggagg caaagctggc tcaccttccg 720 cacgcggatt aatttgcatc tgaaatagga aacaagtgaa agcatatggg ttagatgttg 780 ccatgtgttt tagatggttt cttgcaagca tgcttgtgaa aatgtgttct cggagtgtgt 840 atgccaagag tgcacccatg gtaccaatca tgaatctttg tttcaggttc agtattatgt 900 agttgttcgt tggttataca agttcttggt ccctccagaa ccaccccggc cccctgcccg 960 ttcttgaaat gtaggcatca tgc atg tca aac atg aga tgt gtg gac tgt 1010 Met Ser Asn Met Arg Cys Val Asp Cys 1 5 ggc act tgc ctg ggt cac aca cgg agg cat cct acc ctt ttc tgg gga 1058 Gly Thr Cys Leu Gly His Thr Arg Arg His Pro Thr Leu Phe Trp Gly 10 15 20 25 aag aca ctg cct ggg ctg acc ccg gtg gcg gcc cca gca cct cag cct 1106 Lys Thr Leu Pro Gly Leu Thr Pro Val Ala Ala Pro Ala Pro Gln Pro 30 35 40 gca cag tgt ccc cca ggt tcc gaa gaa gat gct cca gca aca cag cct 1154 Ala Gln Cys Pro Pro Gly Ser Glu Glu Asp Ala Pro Ala Thr Gln Pro 45 50 55 ggg ccc cag ctc gcg gga ccc gac ccc ccg tgg gct ccc gtg ttt tgt 1202 Gly Pro Gln Leu Ala Gly Pro Asp Pro Pro Trp Ala Pro Val Phe Cys 60 65 70 agg aga ctt gcc aga gcc ggg cac att gag ctg tgc aac gcc gtg ggc 1250 Arg Arg Leu Ala Arg Ala Gly His Ile Glu Leu Cys Asn Ala Val Gly 75 80 85 tgc gtc ctt tgg tcc tgt ccc cgc agc cct ggc agg ggg cat gcg gtc 1298 Cys Val Leu Trp Ser Cys Pro Arg Ser Pro Gly Arg Gly His Ala Val 90 95 100 105 ggg cag ggg ctg gag gga ggc ggg ggc tgc cct tgg gcc acc cct cct 1346 Gly Gln Gly Leu Glu Gly Gly Gly Gly Cys Pro Trp Ala Thr Pro Pro 110 115 120 agt ttg gga gga gca gat ttt tgc aat acc aag tat agc cta tgg cag 1394 Ser Leu Gly Gly Ala Asp Phe Cys Asn Thr Lys Tyr Ser Leu Trp Gln 125 130 135 aaa aaa tgt ctg taa atatgttttt aaaggtggat tttgtttaaa aaatcttaat 1449 Lys Lys Cys Leu * 140 gaatgagtct gttgtgtgtc atgccagtga gggacgtcag acttggctca gctcggggag 1509 ccttagccgc ccatgcactg gggacgctcc gctgccgtgc cgcctgcact cctcagggca 1569 gcctcccccg gctctacggg ggccgcgtgg tgccatcccc agggggcatg accagatgcg 1629 tcccaagatg ttgattttta ctgtgtttta taaaatagag tgtagtttac agaaaaagac 1689 tttaaaagtg atctacatga ggaactgtag atgatgtatt tttttcatct tttttgttaa 1749 ctgatttgca ataaaaatga tactgatggt gaaaaaaaaa aaaaaaaaaa cctatgcggc 1809 cgcaagctta 1819 88 4070 DNA Homo sapiens CDS (12)..(2000) 88 tgagtgatgc t atg gag gag atc gac atg caa caa ggc acc tcg tca gta 50 Met Glu Glu Ile Asp Met Gln Gln Gly Thr Ser Ser Val 1 5 10 aaa cca cag gct aat ggt gtt ttg gat gaa aaa tct caa att cag gag 98 Lys Pro Gln Ala Asn Gly Val Leu Asp Glu Lys Ser Gln Ile Gln Glu 15 20 25 cca tgt tgt tca gac ctc ttc ctg ttt cct gac gag agt ggg aat gta 146 Pro Cys Cys Ser Asp Leu Phe Leu Phe Pro Asp Glu Ser Gly Asn Val 30 35 40 45 tcc cag gag tcc ggc ccc acc tat gcc tca ttc tct cac cat ttc atc 194 Ser Gln Glu Ser Gly Pro Thr Tyr Ala Ser Phe Ser His His Phe Ile 50 55 60 agt gat gca atg aca ggt gtg ccc act gag aat gat gac ttt tgc att 242 Ser Asp Ala Met Thr Gly Val Pro Thr Glu Asn Asp Asp Phe Cys Ile 65 70 75 ctt ttt gca cca aaa gca gcc atg cag gag aag gaa gaa gaa cca gtt 290 Leu Phe Ala Pro Lys Ala Ala Met Gln Glu Lys Glu Glu Glu Pro Val 80 85 90 ata aaa atc atg gtt gat gat gca att gtg ata aga gac aat tat ttc 338 Ile Lys Ile Met Val Asp Asp Ala Ile Val Ile Arg Asp Asn Tyr Phe 95 100 105 agt ctg ccc gtt aat aag acc gat acg agc aaa gcc ccc tta cac ttt 386 Ser Leu Pro Val Asn Lys Thr Asp Thr Ser Lys Ala Pro Leu His Phe 110 115 120 125 ccc att cct gtg att cgc tat gtg gtg aag gag gtc tct ctt gtc tgg 434 Pro Ile Pro Val Ile Arg Tyr Val Val Lys Glu Val Ser Leu Val Trp 130 135 140 cat ctt tat gga gga aag gat ttt gga aca gtc cct ccc act tct ccg 482 His Leu Tyr Gly Gly Lys Asp Phe Gly Thr Val Pro Pro Thr Ser Pro 145 150 155 gct aaa agt tat att agt ccc cac agt tcg cct tct cac aca ccc acg 530 Ala Lys Ser Tyr Ile Ser Pro His Ser Ser Pro Ser His Thr Pro Thr 160 165 170 aga cat gga cgt aat aca gta tgt ggg gga aaa gga agg aac cat gac 578 Arg His Gly Arg Asn Thr Val Cys Gly Gly Lys Gly Arg Asn His Asp 175 180 185 ttt tta atg gaa ata cag cta agc aag gtg aag ttt cag cat gaa gtc 626 Phe Leu Met Glu Ile Gln Leu Ser Lys Val Lys Phe Gln His Glu Val 190 195 200 205 tac ccg cca tgc aaa cct gat tgt gat tcc agc ctc tca gaa cac cca 674 Tyr Pro Pro Cys Lys Pro Asp Cys Asp Ser Ser Leu Ser Glu His Pro 210 215 220 gtc tcc cgg cag gtg ttc att gtt cag gat ctt gag att cga gat cgt 722 Val Ser Arg Gln Val Phe Ile Val Gln Asp Leu Glu Ile Arg Asp Arg 225 230 235 ttg gca aca tca caa atg aat aaa ttt tta tac ctg tat tgc agt aaa 770 Leu Ala Thr Ser Gln Met Asn Lys Phe Leu Tyr Leu Tyr Cys Ser Lys 240 245 250 gaa atg cct cga aaa gct cac tcc aac atg ttg aca gtg aaa gcc tta 818 Glu Met Pro Arg Lys Ala His Ser Asn Met Leu Thr Val Lys Ala Leu 255 260 265 cac gtg tgt cca gaa tct ggc agg tcc cca cag gag tgc tgc ttg aga 866 His Val Cys Pro Glu Ser Gly Arg Ser Pro Gln Glu Cys Cys Leu Arg 270 275 280 285 gtg tcg ctg atg ccg ctc cgc ctc aat att gac cag gat gct ttg ttc 914 Val Ser Leu Met Pro Leu Arg Leu Asn Ile Asp Gln Asp Ala Leu Phe 290 295 300 ttc ctg aag gat ttc ttc aca agt ctt tct gca gaa gta gag ctt caa 962 Phe Leu Lys Asp Phe Phe Thr Ser Leu Ser Ala Glu Val Glu Leu Gln 305 310 315 atg act cca gat cca gaa gtt aaa aag tct cct gga gct gat gtc acc 1010 Met Thr Pro Asp Pro Glu Val Lys Lys Ser Pro Gly Ala Asp Val Thr 320 325 330 tgc agt ttg cca agg cat ttg agt acc tca aag gag cca aat ctg gtt 1058 Cys Ser Leu Pro Arg His Leu Ser Thr Ser Lys Glu Pro Asn Leu Val 335 340 345 att tct ttc tct ggg cca aaa cag cct tcc caa aat gat agt gcc aat 1106 Ile Ser Phe Ser Gly Pro Lys Gln Pro Ser Gln Asn Asp Ser Ala Asn 350 355 360 365 tca gtg gaa gtg gtt aat ggc atg gaa gag aag aac ttc tct gct gaa 1154 Ser Val Glu Val Val Asn Gly Met Glu Glu Lys Asn Phe Ser Ala Glu 370 375 380 gaa gca tct ttt agg gat cag cct gtg ttt ttt aga gaa ttt aga ttc 1202 Glu Ala Ser Phe Arg Asp Gln Pro Val Phe Phe Arg Glu Phe Arg Phe 385 390 395 acg tca gaa gtt ccc att cga ctt gat tat cat ggc aaa cat gta tca 1250 Thr Ser Glu Val Pro Ile Arg Leu Asp Tyr His Gly Lys His Val Ser 400 405 410 atg gat cag ggt acg cta gct ggg att ttg att ggt ctg gct cag tta 1298 Met Asp Gln Gly Thr Leu Ala Gly Ile Leu Ile Gly Leu Ala Gln Leu 415 420 425 aac tgc tct gaa cta aag ctc aag agg ctt tcc tat cga cat ggt tta 1346 Asn Cys Ser Glu Leu Lys Leu Lys Arg Leu Ser Tyr Arg His Gly Leu 430 435 440 445 cta ggc gtt gac aaa tta ttc tca tat gca atc act gag tgg ctt aat 1394 Leu Gly Val Asp Lys Leu Phe Ser Tyr Ala Ile Thr Glu Trp Leu Asn 450 455 460 gac att aag aag aac cag cta cca gga atc ctg gga ggt gtt gga cct 1442 Asp Ile Lys Lys Asn Gln Leu Pro Gly Ile Leu Gly Gly Val Gly Pro 465 470 475 atg cat tca cta gta caa tta gta caa ggc cta aag gac ttg gtc tgg 1490 Met His Ser Leu Val Gln Leu Val Gln Gly Leu Lys Asp Leu Val Trp 480 485 490 ctc cca ata gag cag tac cgg aag gat ggc cgc att gtc aga ggg ttt 1538 Leu Pro Ile Glu Gln Tyr Arg Lys Asp Gly Arg Ile Val Arg Gly Phe 495 500 505 cag aga ggc gct gct tcc ttt ggt acc tcg aca gcg atg gct gct cta 1586 Gln Arg Gly Ala Ala Ser Phe Gly Thr Ser Thr Ala Met Ala Ala Leu 510 515 520 525 gaa ctc aca aac aga atg gtt caa acc ata cag gca gct gca gag act 1634 Glu Leu Thr Asn Arg Met Val Gln Thr Ile Gln Ala Ala Ala Glu Thr 530 535 540 gct tat gat atg gtg tct cct ggt acc ctt tct atc gag ccc aag aag 1682 Ala Tyr Asp Met Val Ser Pro Gly Thr Leu Ser Ile Glu Pro Lys Lys 545 550 555 acc aaa agg ttt cct cat cac cgg tta gcc cac cag cca gta gac ctg 1730 Thr Lys Arg Phe Pro His His Arg Leu Ala His Gln Pro Val Asp Leu 560 565 570 agg gaa ggt gtg gcc aag gcc tac agt gtt gtg aaa gag gga atc aca 1778 Arg Glu Gly Val Ala Lys Ala Tyr Ser Val Val Lys Glu Gly Ile Thr 575 580 585 gac acg gct cag acc att tat gaa act gcg gct cga gaa cac gag agc 1826 Asp Thr Ala Gln Thr Ile Tyr Glu Thr Ala Ala Arg Glu His Glu Ser 590 595 600 605 aga ggg gtg act ggt gcc gtg ggc gag gtt ctg cgc cag att cct ccg 1874 Arg Gly Val Thr Gly Ala Val Gly Glu Val Leu Arg Gln Ile Pro Pro 610 615 620 gca gtg gtg aaa cct ctg att gtt gcc aca gaa gca acg tca aac gtg 1922 Ala Val Val Lys Pro Leu Ile Val Ala Thr Glu Ala Thr Ser Asn Val 625 630 635 ctg ggt ggc atg aga aac caa att agg cca gat gtc cgg caa gac gag 1970 Leu Gly Gly Met Arg Asn Gln Ile Arg Pro Asp Val Arg Gln Asp Glu 640 645 650 tca cag aaa tgg cgc cac ggg gat gac tga t ggcttggaac tgacagtgtg 2021 Ser Gln Lys Trp Arg His Gly Asp Asp * 655 660 aagataagga gagtggaacc aggagctcag agtcctgaca gcagcttcag aggaagctcg 2081 tttaatttta ttgtgctcat ctcaggaaca aaagcatttt ttagttaaat aatttaacat 2141 caaaacaaca tgcaaccaaa aacttctgac atttatagtt gatacttgcc tatagaaatg 2201 tttggtggct ggtgtcaaag gtccttaaag catttgctgc caagttagtg gaaggctcac 2261 ttttgttaag atgactgtaa ttctccttgt taccgacgag agatcattgg aagctgcctt 2321 ctaacacttt gtgtagctct gtggagttgg attttcttaa ggtttaaaaa gaatcacagc 2381 ttcggaactt ttaactgaaa atgagagaca gaagccacag gggaagcaaa gcaaatagga 2441 ttttcaatat aaatatcagt gtggaaaaat aacctattct gttgaattta gtgttcatgc 2501 acttgagaac aacattattt ccatttactc cgaaaatcct tctgtggggg tttgagaaag 2561 tgaatgttgc agacatgttc tgttgtgttg cactttatcc tgtgtttatg tgtatgtgtt 2621 tttagattaa ttcaagttgt gtgctatatt tcttgtataa tttacaaagt tacacaaaat 2681 ataaagagca gtaaacttgt ctgaaagttt ttggcaaagg aaggtaactt caatgtaata 2741 gcttccttta agagtacagg aaaatgcatt ctgtaatgaa gtggggccca tgtaattgtt 2801 tatattttca gttttaagca ggtatagtgc aggcttgtta ggaatgtgtg gaagggaaga 2861 ttggaagtga tttttcctct tttaaaagta aacaaaattc ttcaaatatg ccctagttaa 2921 ctatttcagc ataccatttt tacttggtta acagtgtaca ttttgataac ctatcaggaa 2981 tgaataaagt atttttattt aaaggtgata ttgttttatg cttccatgaa tattttgctt 3041 ttcttagagc atattcatag atgcagtact gtgatttacc gcaagataat tgggaacact 3101 ttctcaaaat cgattttggt taatatcagg taaatcatta cctaggagta agagggaaat 3161 tgttgtcaat tcctgacttt agattgatcc agcagaaaga aaaggtggaa ctttgtatat 3221 atccactgtt gaaagttgca tgacctgact tcctgttttc taaagttggg ggaatattat 3281 tgaacttcaa tttcagaact gcatttcaat ttggggcttg gaaaatgtag ttaaatcaat 3341 ttcgttctct aaattttcta agcaggaaag caatgtaaac caaaaatcaa aatgtttaga 3401 atttataaaa atggggttat atagctttta attttagttt cctttttact gccaaaaaac 3461 ttaaaaagac aacagcgtaa ccacctgttt aagcaccgtg ggaccatctc ttattcgggt 3521 agagcctggt cctggcgaca cactaacagg aaggcgtgct gtgttaccgg gaaggcgcct 3581 ctggctgtgg ggtgcgttct gaccaccccg ctcagatgcc agcattttcc atttgccctt 3641 aaggaaactt gctatgtgtg ttaacccagt tatgattagt caaactggaa aacacttgat 3701 caaacttaaa attgtaaaat ctgtctaact tttaaatata ctttccacag ttgtacttaa 3761 gttcaattaa ctacagtata gagaaaaata attattctct tctttgcacc cggagttgca 3821 aacaaattaa gtttacaaat ctcatttaaa catatatctt tgtaatgtaa tctccgcggt 3881 tctttctttg ttctaccctc ctgcacctgt tgtcgatgta atcattttgg gaacagaaac 3941 gttgtgtctc aaaaagattc gttgtcagtt cagccaagat gttctttacc tgagattctg 4001 gaaagatgtt tatctatatc ggaacacttc tacattatta aatgtcctta agctttaaaa 4061 aaaaaaaaa 4070 89 2839 DNA Homo sapiens CDS (681)..(2027) 89 tgggaggagg atgatgtata taactatcta ttcgatgatg aagatacccc accaaaccca 60 aaaaaagaga tctctcgagg atccgaattc gcggccgcgt cgacccgtct caccccagct 120 cctttggctc cgcaccccac ccacacctgc tgcccaccac cccggcagca cctttccctg 180 cccaggcttc agagtgccct gttgctgctg ccactgcccc ccacactcca gggccatgtc 240 agagctccca tctaccctcc accagcatgc cgctcctgaa gatgccccca ccattctcgg 300 ggtgcagcca cccctgcagc gggcactgtg gtgggcactg cagtgggcct ctcctcccac 360 ccccgagctc tcagccactc cctagcactc acagggatcc cgggtgcaag gggcacaagt 420 ttgcacacag tggcctggct tgccagctgc cccagccctg cgaggcagat gaggggctgg 480 gtgaggaaga ggatagcagc tctgagcgaa gctcctgcac ctcatcctcc acccaccaga 540 gagatgggaa gttctgtgac tgctgctact gtgagttctt cggccacaat gcgccacccg 600 ctgccccgac gagtcggaac tataccgaga tccgggagaa gctccgctcg aggctgacca 660 ggcggaaaga ggagctgccc atg aag ggg ggc acc ctg ggc ggg atc cct 710 Met Lys Gly Gly Thr Leu Gly Gly Ile Pro 1 5 10 ggg gag ccc gcc gtg gac cac cga gat gtg gat gag ctg ctg gaa ttc 758 Gly Glu Pro Ala Val Asp His Arg Asp Val Asp Glu Leu Leu Glu Phe 15 20 25 atc aac agc acg gag ccc aaa gtc ccc aac agc gcc agg gcc gcc aag 806 Ile Asn Ser Thr Glu Pro Lys Val Pro Asn Ser Ala Arg Ala Ala Lys 30 35 40 cgg gcc cgg cac aag ctg aaa aag aag gaa aag gag aag gcc cag ttg 854 Arg Ala Arg His Lys Leu Lys Lys Lys Glu Lys Glu Lys Ala Gln Leu 45 50 55 gca gca gaa gct cta aag cag gca aat cgt gtt tct gga agc cgg gag 902 Ala Ala Glu Ala Leu Lys Gln Ala Asn Arg Val Ser Gly Ser Arg Glu 60 65 70 cca agg cct gcc agg gag agg ctc ttg gag tgg ccc gac cgg gaa ctg 950 Pro Arg Pro Ala Arg Glu Arg Leu Leu Glu Trp Pro Asp Arg Glu Leu 75 80 85 90 gat cgg gtc aac agc ttc ctg agc agc cgt ctg cag gag atc aaa aac 998 Asp Arg Val Asn Ser Phe Leu Ser Ser Arg Leu Gln Glu Ile Lys Asn 95 100 105 act gtc aaa gac tcc atc cgt gcc agc ttc agt gtg tgt gag ctc agc 1046 Thr Val Lys Asp Ser Ile Arg Ala Ser Phe Ser Val Cys Glu Leu Ser 110 115 120 atg gac agc aat ggc ttc tct aag gag ggg gct gct gag cct gag cct 1094 Met Asp Ser Asn Gly Phe Ser Lys Glu Gly Ala Ala Glu Pro Glu Pro 125 130 135 cag agt cta ccc ccc tca aac ctc agt ggc tcc tca gag cag cag cct 1142 Gln Ser Leu Pro Pro Ser Asn Leu Ser Gly Ser Ser Glu Gln Gln Pro 140 145 150 gac atc aac ctt gac ctg tcc cct ttg act ttg ggc tcc cct cag aac 1190 Asp Ile Asn Leu Asp Leu Ser Pro Leu Thr Leu Gly Ser Pro Gln Asn 155 160 165 170 cac acg tta caa gct cca ggc gag cca gcc cca cca tgg gca gaa atg 1238 His Thr Leu Gln Ala Pro Gly Glu Pro Ala Pro Pro Trp Ala Glu Met 175 180 185 aga ggc ccc cac cca cca tgg aca gag gtg agg ggg ccc cct ccc ggt 1286 Arg Gly Pro His Pro Pro Trp Thr Glu Val Arg Gly Pro Pro Pro Gly 190 195 200 atc gtc ccc gag aac ggg ctc gtg agg aga ctc aac acc gtg ccc aac 1334 Ile Val Pro Glu Asn Gly Leu Val Arg Arg Leu Asn Thr Val Pro Asn 205 210 215 cta tcc cgg gtg atc tgg gtc aag aca ccc aag ccg ggc tac ccc agc 1382 Leu Ser Arg Val Ile Trp Val Lys Thr Pro Lys Pro Gly Tyr Pro Ser 220 225 230 tcc gag gag cca agc tca aag gaa gtt ccc agt tgc aag cag gag ctg 1430 Ser Glu Glu Pro Ser Ser Lys Glu Val Pro Ser Cys Lys Gln Glu Leu 235 240 245 250 cct gag cct gtg tcc tca ggt ggg aag cca cag aag ggc aag agg cag 1478 Pro Glu Pro Val Ser Ser Gly Gly Lys Pro Gln Lys Gly Lys Arg Gln 255 260 265 ggc agt cag gcc aag aag agc gag gca agc cca gcc ccc cgg ccc cca 1526 Gly Ser Gln Ala Lys Lys Ser Glu Ala Ser Pro Ala Pro Arg Pro Pro 270 275 280 gcc agc cta gag gtt ccc agt gcc aag ggc cag gtc gct ggc ccc aag 1574 Ala Ser Leu Glu Val Pro Ser Ala Lys Gly Gln Val Ala Gly Pro Lys 285 290 295 cag cca ggc agg gtc cta gag ctt ccc aaa gta ggc agc tgt gct gag 1622 Gln Pro Gly Arg Val Leu Glu Leu Pro Lys Val Gly Ser Cys Ala Glu 300 305 310 gct gga gag ggg agc cgg ggg agc cgg cca gga cca ggt tgg gct ggc 1670 Ala Gly Glu Gly Ser Arg Gly Ser Arg Pro Gly Pro Gly Trp Ala Gly 315 320 325 330 agt ccc aaa act gag aag gag aag ggc agc tcc tgg cga aac tgg cca 1718 Ser Pro Lys Thr Glu Lys Glu Lys Gly Ser Ser Trp Arg Asn Trp Pro 335 340 345 ggc gag gcc aag gca cgg cct cag gag cag gag tct gtg cag ccc cca 1766 Gly Glu Ala Lys Ala Arg Pro Gln Glu Gln Glu Ser Val Gln Pro Pro 350 355 360 ggc cca gca agg cca cag agc ttg ccc cag ggc aag ggc cgc agc cgc 1814 Gly Pro Ala Arg Pro Gln Ser Leu Pro Gln Gly Lys Gly Arg Ser Arg 365 370 375 cgg agc cgc aac aag cag gag aag cca gcc tcc tcc ttg gac gat gtg 1862 Arg Ser Arg Asn Lys Gln Glu Lys Pro Ala Ser Ser Leu Asp Asp Val 380 385 390 ttc ctg ccc aag gac atg gac ggg gtg gag atg gat gag act gac cga 1910 Phe Leu Pro Lys Asp Met Asp Gly Val Glu Met Asp Glu Thr Asp Arg 395 400 405 410 gag gtg gag tac ttt aag agg ttc tgt ttg gat tct gca aag cag act 1958 Glu Val Glu Tyr Phe Lys Arg Phe Cys Leu Asp Ser Ala Lys Gln Thr 415 420 425 cgt cag aaa gtt gct gtg aac tgg acc aac ttc agc ctc aag aaa acc 2006 Arg Gln Lys Val Ala Val Asn Trp Thr Asn Phe Ser Leu Lys Lys Thr 430 435 440 act cct agc aca gct cag tga gg ccctgcccag gctgagctgc ttcagggcat 2059 Thr Pro Ser Thr Ala Gln * 445 cctgaggccc tgactgccag ctgaaggcgt ataatttttc cctccgtgtg ccccacctac 2119 ccgtccaaaa ctgagaagga gaagggcagc tcctggcgaa actggccagg cgaggccaag 2179 gcacggcctc aggagcagga gtctgtgcag cccccaggcc cagcaaggcc acagagcttg 2239 ccccagggcc agggccgcag ccgccggagc cgcaacaagc aggagaagcc agcctcctcc 2299 ttggacgatg tgttcctgcc caaggacatg gacggggtgg agatggatga gactgaccga 2359 gaggcagggc agtcaggcca agaagagctg gcccaacact gctctctttg tgtttggttt 2419 ttttgttttt gtttttattt tgtttttttc caattcttta cttttgatac tgtgaagatc 2479 tttcgtgccg aaagataaag caacatttgg acacagagtt ggcatgttgg tgatttgtgg 2539 gtctgggcgg ggagggagtt gagggtgtgc tcagaagcat gggctctccc ttagtcacta 2599 accctagcat gcaccatgca tcagcagttt ggtgctattg tcccatttta caggtgagga 2659 aactaaagcc gataggaaag tgactcagct caacttagtc tggctgatta gcattgagcg 2719 cagactggta tgattatggc atctgtgccc ttttctcctt ttgggaggtc tctggtatgt 2779 gagcctgggg cagccccttc cccactcttt cctgtttccc tctttgcaag atgggtgagt 2839 90 3813 DNA Homo sapiens CDS (183)..(2495) 90 agagtaaagt gcagcctctc cagacactgg ggccccagtg gctgtgggcg aaggtaatcc 60 aggcctgggt acgattccgg gccctccttc gacttcccag cggttgctgg taggaggagt 120 tggcggaacg acttggaact cctttataag tgtcagctgt gagattttaa tttgatttga 180 aa atg agt aag tgc aga aag aca cca gtt cag cag cta gca agt ccc 227 Met Ser Lys Cys Arg Lys Thr Pro Val Gln Gln Leu Ala Ser Pro 1 5 10 15 gcg tca ttc agc cca gat att ctt gct gac att ttt gaa ctc ttt gcc 275 Ala Ser Phe Ser Pro Asp Ile Leu Ala Asp Ile Phe Glu Leu Phe Ala 20 25 30 aag aac ttt tct tat ggc aag cca ctt aat aat gag tgg cag tta cca 323 Lys Asn Phe Ser Tyr Gly Lys Pro Leu Asn Asn Glu Trp Gln Leu Pro 35 40 45 gat ccc agt gag att ttc acc tgt gac cac act gaa ttt aat gca ttt 371 Asp Pro Ser Glu Ile Phe Thr Cys Asp His Thr Glu Phe Asn Ala Phe 50 55 60 ctt gat ttg aag aac tcc cta aat gaa gta aaa aac cta ctg agt gat 419 Leu Asp Leu Lys Asn Ser Leu Asn Glu Val Lys Asn Leu Leu Ser Asp 65 70 75 aag aaa ctg gat gag tgg cat gag cac act gct ttc act aat aaa gca 467 Lys Lys Leu Asp Glu Trp His Glu His Thr Ala Phe Thr Asn Lys Ala 80 85 90 95 ggg aaa atc att tct cat gtt aga aaa tct gtg aat gct gaa ctt tgt 515 Gly Lys Ile Ile Ser His Val Arg Lys Ser Val Asn Ala Glu Leu Cys 100 105 110 act caa gca tgg tgt aag ttc cat gag att ttg tgc agc ttt cca ctt 563 Thr Gln Ala Trp Cys Lys Phe His Glu Ile Leu Cys Ser Phe Pro Leu 115 120 125 att cca cag gaa gct ttt cag aat gga aaa ctg aat tct cta cac ctt 611 Ile Pro Gln Glu Ala Phe Gln Asn Gly Lys Leu Asn Ser Leu His Leu 130 135 140 tgt gaa gct cca gga gct ttt ata gct agt ctc aac cac tac tta aaa 659 Cys Glu Ala Pro Gly Ala Phe Ile Ala Ser Leu Asn His Tyr Leu Lys 145 150 155 tcc cat cgg ttt cct tgt cat tgg agt tgg gta gcg aat act ctg aat 707 Ser His Arg Phe Pro Cys His Trp Ser Trp Val Ala Asn Thr Leu Asn 160 165 170 175 cca tac cat gaa gca aat gac gac ctc atg atg att atg gat gac cgg 755 Pro Tyr His Glu Ala Asn Asp Asp Leu Met Met Ile Met Asp Asp Arg 180 185 190 ctt att gca aat acc ttg cac tgg tgg tac ttt ggt cca gat aac act 803 Leu Ile Ala Asn Thr Leu His Trp Trp Tyr Phe Gly Pro Asp Asn Thr 195 200 205 ggt gat atc atg acc ctg aaa ttc ttg act gga ctt cag aat ttc ata 851 Gly Asp Ile Met Thr Leu Lys Phe Leu Thr Gly Leu Gln Asn Phe Ile 210 215 220 agc agc atg gct act gtt cac ttg gtc act gca gat ggg agt ttt gat 899 Ser Ser Met Ala Thr Val His Leu Val Thr Ala Asp Gly Ser Phe Asp 225 230 235 tgc caa gga aac cca ggt gaa caa gaa gct tta gtt tct tct ttg cat 947 Cys Gln Gly Asn Pro Gly Glu Gln Glu Ala Leu Val Ser Ser Leu His 240 245 250 255 tac tgt gaa gtt gtc act gct ctg acc act ctt gga aac ggt ggc tct 995 Tyr Cys Glu Val Val Thr Ala Leu Thr Thr Leu Gly Asn Gly Gly Ser 260 265 270 ttt gtt cta aag atg ttt act atg ttt gaa cat tgt tcc ata aac ttg 1043 Phe Val Leu Lys Met Phe Thr Met Phe Glu His Cys Ser Ile Asn Leu 275 280 285 atg tac ctg cta aac tgt tgt ttt gac caa gtc cat gtt ttc aaa cct 1091 Met Tyr Leu Leu Asn Cys Cys Phe Asp Gln Val His Val Phe Lys Pro 290 295 300 gct act agc aag gca gga aac tcc gaa gtc tat gtg gtt tgc ctc cac 1139 Ala Thr Ser Lys Ala Gly Asn Ser Glu Val Tyr Val Val Cys Leu His 305 310 315 tat aag ggg aga gag gcc atc cat cct ctg tta tct aag atg acc ttg 1187 Tyr Lys Gly Arg Glu Ala Ile His Pro Leu Leu Ser Lys Met Thr Leu 320 325 330 335 aat ttt ggg act gaa atg aaa agg aaa gcc ctt ttt ccc cat cat gtg 1235 Asn Phe Gly Thr Glu Met Lys Arg Lys Ala Leu Phe Pro His His Val 340 345 350 att cct gat tct ttt ctt aag aga cat gaa gaa tgt tgt gtg ttc ttt 1283 Ile Pro Asp Ser Phe Leu Lys Arg His Glu Glu Cys Cys Val Phe Phe 355 360 365 cat aaa tat cag cta gag act att tct gaa aac att cgt cta ttt gag 1331 His Lys Tyr Gln Leu Glu Thr Ile Ser Glu Asn Ile Arg Leu Phe Glu 370 375 380 tgc atg gga aag gcg gaa caa gaa aag ctg aat aat tta agg gat tgt 1379 Cys Met Gly Lys Ala Glu Gln Glu Lys Leu Asn Asn Leu Arg Asp Cys 385 390 395 gct ata caa tat ttt atg caa aaa ttt caa ctg aaa cat ctt tcc aga 1427 Ala Ile Gln Tyr Phe Met Gln Lys Phe Gln Leu Lys His Leu Ser Arg 400 405 410 415 aat aat tgg cta gta aaa aaa tct agt att ggt tgt agt aca aat aca 1475 Asn Asn Trp Leu Val Lys Lys Ser Ser Ile Gly Cys Ser Thr Asn Thr 420 425 430 aaa tgg ttt ggg cag agg aac aaa tat ttt aaa act tat aat gaa agg 1523 Lys Trp Phe Gly Gln Arg Asn Lys Tyr Phe Lys Thr Tyr Asn Glu Arg 435 440 445 aag atg cta gaa gcc ctt tca tgg aaa gat aaa gta gcc aaa gga tac 1571 Lys Met Leu Glu Ala Leu Ser Trp Lys Asp Lys Val Ala Lys Gly Tyr 450 455 460 ttt aat agt tgg gct gaa gaa cat ggt gta tat cat cct ggg cag agt 1619 Phe Asn Ser Trp Ala Glu Glu His Gly Val Tyr His Pro Gly Gln Ser 465 470 475 tct att tta gaa gga aca gct tcc aat ctt gag tgt cac tta tgg cat 1667 Ser Ile Leu Glu Gly Thr Ala Ser Asn Leu Glu Cys His Leu Trp His 480 485 490 495 att ttg gag gga aag aaa ctg cca aag gta aaa tgt tct cct ttt tgc 1715 Ile Leu Glu Gly Lys Lys Leu Pro Lys Val Lys Cys Ser Pro Phe Cys 500 505 510 aat ggt gaa att tta aaa act ctt aat gaa gca att gaa aag tca tta 1763 Asn Gly Glu Ile Leu Lys Thr Leu Asn Glu Ala Ile Glu Lys Ser Leu 515 520 525 gga gga gct ttt aat ttg gat tcc aag ttt agg cca aaa cag cag tat 1811 Gly Gly Ala Phe Asn Leu Asp Ser Lys Phe Arg Pro Lys Gln Gln Tyr 530 535 540 tct tgt tct tgt cat gtt ttt tct gaa gaa ctg ata ttt tcc gag ttg 1859 Ser Cys Ser Cys His Val Phe Ser Glu Glu Leu Ile Phe Ser Glu Leu 545 550 555 tgt agc ctt act gag tgc ctt cag gat gag cag gtt gta gta ccc agc 1907 Cys Ser Leu Thr Glu Cys Leu Gln Asp Glu Gln Val Val Val Pro Ser 560 565 570 575 aat caa ata aag tgc ctg ctg gtg ggc ttt tcg act ctc cgt aat atc 1955 Asn Gln Ile Lys Cys Leu Leu Val Gly Phe Ser Thr Leu Arg Asn Ile 580 585 590 aaa atg cat ata ccg ttg gaa gtt cga ctc cta gaa tca gct gaa ctc 2003 Lys Met His Ile Pro Leu Glu Val Arg Leu Leu Glu Ser Ala Glu Leu 595 600 605 aca act ttt agc tgt tca ttg ctt cat gat gga gat cca act tac cag 2051 Thr Thr Phe Ser Cys Ser Leu Leu His Asp Gly Asp Pro Thr Tyr Gln 610 615 620 cgt tta ttt ttg gac tgc ctt cta cat tca ttg cgg gag ctt cat aca 2099 Arg Leu Phe Leu Asp Cys Leu Leu His Ser Leu Arg Glu Leu His Thr 625 630 635 gga gat gtt atg att ttg cct gta ctt tct tgc ttc aca aga ttt atg 2147 Gly Asp Val Met Ile Leu Pro Val Leu Ser Cys Phe Thr Arg Phe Met 640 645 650 655 gct ggt ttg atc ttt gta ctc cac agt tgt ttt aga ttc atc act ttt 2195 Ala Gly Leu Ile Phe Val Leu His Ser Cys Phe Arg Phe Ile Thr Phe 660 665 670 gtt tgt ccc aca tcc tct gat ccc ctg agg acc tgc gca gtc ctg cta 2243 Val Cys Pro Thr Ser Ser Asp Pro Leu Arg Thr Cys Ala Val Leu Leu 675 680 685 tgt gtt ggt tat cag gac ctt cca aat cca gtt ttc cga tat ttg cag 2291 Cys Val Gly Tyr Gln Asp Leu Pro Asn Pro Val Phe Arg Tyr Leu Gln 690 695 700 agt gtg aat gaa ttg ttg agc act ttg ctc aac tct gac tca ccc cag 2339 Ser Val Asn Glu Leu Leu Ser Thr Leu Leu Asn Ser Asp Ser Pro Gln 705 710 715 cag gtt tta cag ttt gtg cca atg gag gta ctc ctt aag ggg gcc ctg 2387 Gln Val Leu Gln Phe Val Pro Met Glu Val Leu Leu Lys Gly Ala Leu 720 725 730 735 ctt gat ttt ttg tgg gat ttg aat gct gcc att gct aaa agg cat ttg 2435 Leu Asp Phe Leu Trp Asp Leu Asn Ala Ala Ile Ala Lys Arg His Leu 740 745 750 cat ttc att att caa aga gag aga gaa gaa att atc aac agc ctt cag 2483 His Phe Ile Ile Gln Arg Glu Arg Glu Glu Ile Ile Asn Ser Leu Gln 755 760 765 tta caa aac tga aca tatgctttct gagattcaac tttatgattt cttataattt 2538 Leu Gln Asn * 770 gcccagtatt tgcatcctgt tgctctatta atttaaaaac cttttatttt ggggaaaggc 2598 caacatttgc atcattcaaa gtctcattaa ttctggaaaa ccatccattc tgatctctag 2658 ggtatataca cccacaggca tagagctctt ccacgtggtg gaatctatgc aatgatagat 2718 attcacactc taaatatgag gtgtgtgtat gtgtatgggt ggccacagcc atgcttacct 2778 atgccattta gttggtctta cttaatctgc ttaagatttg catctgtgta cctttgttca 2838 gattagtttt ttttttttcc agccgatttc ctcttagtgg ctaatgctgt tagtgaattt 2898 tccaactaat ttcctctcat tggttaatgt tgttaatgaa ttgagagagg taattgagga 2958 aaggaaatga gtaaatcact gttcagcaac actgatttcc gttaacacat cagttatgaa 3018 tttcagggaa ttcatctcgc cagattcttg ataacatgcc attcattgcc cttaggtgat 3078 tgaccctatt ttcttacatg gctcaaataa aactagtatg ctgttgtatg aatcttttac 3138 tgaccacacc atccaactat aaaaatataa cgggacagct ttaaaccaaa gatcatgttt 3198 agaacaatga aaaattattt gttgtatcta atacacgcct gtattgtgaa aagcttcatt 3258 tagcaatgat gtaataattt ttaacttcca ggaaataatc tgtgaatgga aagatttttt 3318 aagattttga gatagtgttt agtctcatgt tgggaacaca tgaatgtgat gaacatagtg 3378 aatactaaag aaaacgcttc agactttcag aatgatggtt cagaatttaa aatttttaat 3438 cttttctaat ttcttttttt cagtgtgaaa atagcacttt accaaaagat tagccatgaa 3498 atggttattt tgccagttac atttgatttc ttttgtatct gcaatgtaat gagttatttt 3558 atttcttctg tatttgcagt gtaatgagtt tttgtggcaa agtgtattaa gcaatttttc 3618 attatcttga agttccacaa agtggagaat atttatattc tcacatgcat tttaggcact 3678 tttgatatgt gaaaatagat gtattttctg atgcatttgg ttaataaata ttaatctgaa 3738 cattttcatg ttctttgcta ttttgaattc cattatagat tcatgaataa agtcattact 3798 agagaaaaaa aaaaa 3813 91 3251 DNA Homo sapiens CDS (105)..(2177) 91 cggtcgacga tttcgtcaaa tgttgtttat caggaattct tattggttta tggaagtaac 60 accggttggt gattggctat accttgttga gctataagaa ccac atg ccc tgg gaa 116 Met Pro Trp Glu 1 gaa cca gca ggt gag aag ccc agt tgc tct cac agt cag aag gcg ttc 164 Glu Pro Ala Gly Glu Lys Pro Ser Cys Ser His Ser Gln Lys Ala Phe 5 10 15 20 cac atg gag cct gcc cag aag ccc tgc ttc acc act gac atg gtg aca 212 His Met Glu Pro Ala Gln Lys Pro Cys Phe Thr Thr Asp Met Val Thr 25 30 35 tgg gcc ctc ctc tgc atc tct gca gag act gtg cgt ggg gag gct cct 260 Trp Ala Leu Leu Cys Ile Ser Ala Glu Thr Val Arg Gly Glu Ala Pro 40 45 50 tca cag cct agg ggc atc cct cac cgc tcg ccc gtc agt gtg gat gac 308 Ser Gln Pro Arg Gly Ile Pro His Arg Ser Pro Val Ser Val Asp Asp 55 60 65 ctg tgg ctg gag aag aca cag aga aag aag ttg cag aag cag gcc cac 356 Leu Trp Leu Glu Lys Thr Gln Arg Lys Lys Leu Gln Lys Gln Ala His 70 75 80 atc gaa agg agg ctg cac ata ggg gca gtg cac aaa gat gga gtc aag 404 Ile Glu Arg Arg Leu His Ile Gly Ala Val His Lys Asp Gly Val Lys 85 90 95 100 tgc tgg aga aag acg atc att acc tct cca gag tct ttg aat ctc cct 452 Cys Trp Arg Lys Thr Ile Ile Thr Ser Pro Glu Ser Leu Asn Leu Pro 105 110 115 aga aga agc cat cca ctc tcc cag agt gct cca acg gga ctg aac cac 500 Arg Arg Ser His Pro Leu Ser Gln Ser Ala Pro Thr Gly Leu Asn His 120 125 130 atg ggc tgg cca gag cac aca cca ggc act gcc atg cct gat gga gct 548 Met Gly Trp Pro Glu His Thr Pro Gly Thr Ala Met Pro Asp Gly Ala 135 140 145 ctg gac aca gct gtc tgc gct gac gaa gtg ggg agc gag gag gac ctg 596 Leu Asp Thr Ala Val Cys Ala Asp Glu Val Gly Ser Glu Glu Asp Leu 150 155 160 tat gat gac ctg cac agc tcc agc cac cac tac agc cac cct gga ggg 644 Tyr Asp Asp Leu His Ser Ser Ser His His Tyr Ser His Pro Gly Gly 165 170 175 180 ggt ggg gag cag ctg gct atc aat gag ctc atc agc gat ggc agt gtg 692 Gly Gly Glu Gln Leu Ala Ile Asn Glu Leu Ile Ser Asp Gly Ser Val 185 190 195 gtc tgc gct gaa gca ctc tgg gac cat gtc acc atg gac gac cag gag 740 Val Cys Ala Glu Ala Leu Trp Asp His Val Thr Met Asp Asp Gln Glu 200 205 210 ctg ggc ttc aaa gct ggg gac gtc atc gaa gtg atg gat gcc acc aac 788 Leu Gly Phe Lys Ala Gly Asp Val Ile Glu Val Met Asp Ala Thr Asn 215 220 225 aga gag tgg tgg tgg ggc cgg gtc gcc gat ggc gag ggc tgg ttt cca 836 Arg Glu Trp Trp Trp Gly Arg Val Ala Asp Gly Glu Gly Trp Phe Pro 230 235 240 gcc agc ttc gtt cgg ctg agg gtg aat cag gac gag ccc gcg gat gac 884 Ala Ser Phe Val Arg Leu Arg Val Asn Gln Asp Glu Pro Ala Asp Asp 245 250 255 260 gac gcc cct ctg gcc ggg aac agc gga gcg gag gac ggc ggg gcg gag 932 Asp Ala Pro Leu Ala Gly Asn Ser Gly Ala Glu Asp Gly Gly Ala Glu 265 270 275 gcg cag agc agc aag gac cag atg cgg acc aac gtc atc aac gag atc 980 Ala Gln Ser Ser Lys Asp Gln Met Arg Thr Asn Val Ile Asn Glu Ile 280 285 290 ctc agc act gag cgg gac tac atc aag cac ctg cgc gac atc tgc gag 1028 Leu Ser Thr Glu Arg Asp Tyr Ile Lys His Leu Arg Asp Ile Cys Glu 295 300 305 ggc tac gtc cgg cag tgc cgc aag cgc gca gac atg ttc agc gag gag 1076 Gly Tyr Val Arg Gln Cys Arg Lys Arg Ala Asp Met Phe Ser Glu Glu 310 315 320 cag ctg cgt acc atc ttc ggg aac atc gag gac atc tac cgc tgc cag 1124 Gln Leu Arg Thr Ile Phe Gly Asn Ile Glu Asp Ile Tyr Arg Cys Gln 325 330 335 340 aag gcc ttc gtg aag gcc ctg gag cag agg ttc aac cgc gag cgc cca 1172 Lys Ala Phe Val Lys Ala Leu Glu Gln Arg Phe Asn Arg Glu Arg Pro 345 350 355 cac ctg agc gag ctg ggt gcc tgc ttc ctg gag cat caa gcc gac ttc 1220 His Leu Ser Glu Leu Gly Ala Cys Phe Leu Glu His Gln Ala Asp Phe 360 365 370 cag atc tac tcg gag tac tgc aat aac cac ccc aac gcc tgc gtg gag 1268 Gln Ile Tyr Ser Glu Tyr Cys Asn Asn His Pro Asn Ala Cys Val Glu 375 380 385 ctc tcc cgg ctc acc aag ctc agc aag tac gtg tac ttc ttc gag gcc 1316 Leu Ser Arg Leu Thr Lys Leu Ser Lys Tyr Val Tyr Phe Phe Glu Ala 390 395 400 tgc cgg ctg ctg cag aag atg att gac atc tcc ctg gat ggc ttc ctg 1364 Cys Arg Leu Leu Gln Lys Met Ile Asp Ile Ser Leu Asp Gly Phe Leu 405 410 415 420 ctg act ccg gtg cag aag atc tgc aag tac cct ctg cag ctg gcc gag 1412 Leu Thr Pro Val Gln Lys Ile Cys Lys Tyr Pro Leu Gln Leu Ala Glu 425 430 435 ctg ctc aaa tac acg cac ccc cag cac agg gac ttc aag gat gtt gaa 1460 Leu Leu Lys Tyr Thr His Pro Gln His Arg Asp Phe Lys Asp Val Glu 440 445 450 gcc gcc ttg cat gcc atg aag aac gtg gcc cag ctc atc aac gag cgg 1508 Ala Ala Leu His Ala Met Lys Asn Val Ala Gln Leu Ile Asn Glu Arg 455 460 465 aag cgg aga ctt gag aac atc gac aag att gct cag tgg cag agc tcc 1556 Lys Arg Arg Leu Glu Asn Ile Asp Lys Ile Ala Gln Trp Gln Ser Ser 470 475 480 ata gag gac tgg gag gga gaa gat ctc ttg gtc agg agc tca gaa ctc 1604 Ile Glu Asp Trp Glu Gly Glu Asp Leu Leu Val Arg Ser Ser Glu Leu 485 490 495 500 atc tac tcg ggg gag ctg act cga gtt aca cag cct caa gcc aaa agc 1652 Ile Tyr Ser Gly Glu Leu Thr Arg Val Thr Gln Pro Gln Ala Lys Ser 505 510 515 cag cag cga atg ttc ttt ctc ttt gac cac cag ctc atc tac tgt aag 1700 Gln Gln Arg Met Phe Phe Leu Phe Asp His Gln Leu Ile Tyr Cys Lys 520 525 530 aag gac ctg ctc cgc cgc gac gtg ttg tac tac aag ggc cgg ctg gac 1748 Lys Asp Leu Leu Arg Arg Asp Val Leu Tyr Tyr Lys Gly Arg Leu Asp 535 540 545 atg gac ggc ctg gag gtg gtg gac ctg gag gac ggg aag gac aga gac 1796 Met Asp Gly Leu Glu Val Val Asp Leu Glu Asp Gly Lys Asp Arg Asp 550 555 560 ctc cat gtg agc atc aag aac gcc ttc cgg ctg cac cgt ggc gcc aca 1844 Leu His Val Ser Ile Lys Asn Ala Phe Arg Leu His Arg Gly Ala Thr 565 570 575 580 ggg gac agc cac ctg ctg tgc acc agg aag cct gag cag aag cag cgc 1892 Gly Asp Ser His Leu Leu Cys Thr Arg Lys Pro Glu Gln Lys Gln Arg 585 590 595 tgg ctc aag gcc ttt gcc agg gag agg gag cag gtg cag ctg gac cag 1940 Trp Leu Lys Ala Phe Ala Arg Glu Arg Glu Gln Val Gln Leu Asp Gln 600 605 610 gag aca ggc ttc tcc atc act gaa ctg cag agg aag cag gcc atg ctg 1988 Glu Thr Gly Phe Ser Ile Thr Glu Leu Gln Arg Lys Gln Ala Met Leu 615 620 625 aat gcc agc aag cag cag gtc aca ggg aag ccc aaa gct gtt ggc cgg 2036 Asn Ala Ser Lys Gln Gln Val Thr Gly Lys Pro Lys Ala Val Gly Arg 630 635 640 ccc tgc tac ctg acg cgc cag aag cac cca gcc ctg ccc agc aac cgg 2084 Pro Cys Tyr Leu Thr Arg Gln Lys His Pro Ala Leu Pro Ser Asn Arg 645 650 655 660 ccc cag cag cag gtc ctg gtg ctg gcg gag ccc agg cgc aag cca tct 2132 Pro Gln Gln Gln Val Leu Val Leu Ala Glu Pro Arg Arg Lys Pro Ser 665 670 675 acc ttc tgg cac agc atc agc cgg ctg gca ccc ttc cgc aag tga act 2180 Thr Phe Trp His Ser Ile Ser Arg Leu Ala Pro Phe Arg Lys * 680 685 690 ggtccctgcc tgacagcacc tgctgggcct tcctgccagt ggcccccagt ttttcttccc 2240 cgaggcccac tcggcctggc cttcctctgc ctgcaagtga gcagggatgg gctggggagt 2300 tgcttgtgcc accaagacgt gccaggtctg tactcctgtt gtctttttcc ctgctcctgg 2360 tgccctgaag agaccagcaa gggggcagac cccgcactcg ccacaccgcc gctgcagctt 2420 gggccccatc cgccctctgg acctgtgtag ggcctcactg ctggagcggg gaaaccgcag 2480 ctcagcccag gcccagctgg ggagaaggcg ctacctgcgt gggaccctct tctctggaaa 2540 cctaatcctc ctttcatttc ctctgggcag gactctctgg ccttctgtgg cctgcaatgc 2600 caggccatgt gcccctctgc cctctagttc tccaagtccc cagcccggcc agtggtgcca 2660 ggcagcttgc cacttgggag ggcagaagcc aggaattcca cacccttgtg ttgcgcccgg 2720 agcccgccct tcgcctccca gcccctcaag acaccgctgg ctgctggaca ccctcttcac 2780 ttgtgtgtgt gtgtgtagcg gaaaaggaca agacggtgca gtcggctgca tactcccagt 2840 cgggagtgtg gtcagtctgc ctgctgctgt gcggtagctc cagaaccacc tcgttcctgg 2900 ttttgtttgg attttggcat cttgtttttc taacaacaaa caatggagaa aaagaattga 2960 ttcttagtga cacagaagat tgccttacgc tcgtgagcgt gagaagccat aagagagaga 3020 ccgaattctg tggctcagca cacaggactg acccacagcc caggcagcgg gtgtgtggag 3080 atggcgccct gtcctgccaa ggggcgccag gagcagagcc agggcctggc gagctggcgt 3140 ggagcccaca ggattcagca gcatggacag tcactcttgc actattcctt ctccaagcca 3200 gaaaccacat ttaatttcat aaataaattt atgaaaagta aaaaaaaaaa a 3251 

What is claimed is:
 1. An isolated polynucleotide comprising a nucleotide sequence selected from the group consisting of SEQ ID NO: 1-91, a mature protein coding portion of SEQ ID NO: 1-91, an active domain of SEQ ID NO: 1-91, and complementary sequences thereof.
 2. An isolated polynucleotide encoding a polypeptide with biological activity, wherein said polynucleotide hybridizes to the polynucleotide of claim 1 under stringent hybridization conditions.
 3. An isolated polynucleotide encoding a polypeptide with biological activity, wherein said polynucleotide has greater than about 90% sequence identity with the polynucleotide of claim
 1. 4. The polynucleotide of claim 1 wherein said polynucleotide is DNA.
 5. An isolate d polynucleotide of claim 1 wherein said polynucleotide comprises the complementary sequences.
 6. A vector comprising the polynucleotide of claim
 1. 7. An expression vector comprising the polynucleotide of claim
 1. 8. A host cell genetically engineered to comprise the polynucleotide of claim
 1. 9. A host cell genetically engineered to comprise the polynucleotide of claim 1 operatively associated with a regulatory sequence that modulates expression of the polynucleotide in the host cell.
 10. An isolated polypeptide, wherein the polypeptide is selected from the group consisting of: (a) a polypeptide encoded by any one of the polynucleotides of claim 1; and (b) a polypeptide encoded by a polynucleotide hybridizing under stringent conditions with any one of SEQ ID NO: 1-
 91. 11. A composition comprising the polypeptide of claim 10 and a carrier.
 12. An antibody directed against the polypeptide of claim
 10. 13. A method for detecting the polynucleotide of claim 1 in a sample, comprising: a) contacting the sample with a compound that binds to and forms a complex with the polynucleotide of claim 1 for a period sufficient to form the complex; and b) detecting the complex, so that if a complex is detected, the polynucleotide of claim 1 is detected.
 14. A method for detecting the polynucleotide of claim 1 in a sample, comprising: a) contacting the sample under stringent hybridization conditions with nucleic acid primers that anneal to the polynucleotide of claim 1 under such conditions; b) amplifying a product comprising at least a portion of the polynucleotide of claim 1; and c) detecting said product and thereby the polynucleotide of claim 1 in the sample.
 15. The method of claim 14, wherein the polynucleotide is an RNA molecule and the method further comprises reverse transcribing an annealed RNA molecule into a cDNA polynucleotide.
 16. A method for detecting the polypeptide of claim 10 in a sample, comprising: a) contacting the sample with a compound that binds to and forms a complex with the polypeptide under conditions and for a period sufficient to form the complex; and b) detecting formation of the complex, so that if a complex formation is detected, the polypeptide of claim 10 is detected.
 17. A method for identifying a compound that binds to the polypeptide of claim 10, comprising: a) contacting the compound with the polypeptide of claim 10 under conditions sufficient to form a polypeptide/compound complex; and b) detecting the complex, so that if the polypeptide/compound complex is detected, a compound that binds to the polypeptide of claim 10 is identified.
 18. A method for identifying a compound that binds to the polypeptide of claim 10, comprising: a) contacting the compound with the polypeptide of claim 10, in a cell, under conditions sufficient to form a polypeptide/compound complex, wherein the complex drives expression of a reporter gene sequence in the cell; and b) detecting the complex by detecting reporter gene sequence expression, so that if the polypeptide/compound complex is detected, a compound that binds to the polypeptide of claim 10 is identified.
 19. A method of producing the polypeptide of claim 10, comprising, a) culturing a host cell comprising a polynucleotide sequence selected from the group consisting of a polynucleotide sequence of SEQ ID NO: 1-91, a mature protein coding portion of SEQ ID NO: 1-91, an active domain of SEQ ID NO: 1-91, complementary sequences thereof and a polynucleotide sequence hybridizing under stringent conditions to SEQ ID NO: 1-91, under conditions sufficient to express the polypeptide in said cell; and b) isolating the polypeptide from the cell culture or cells of step (a).
 20. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of any one of the polypeptides from the Sequence Listing, the mature protein portion thereof, or the active domain thereof.
 21. The polypeptide of claim 20 wherein the polypeptide is provided on a polypeptide array.
 22. A collection of polynucleotides, wherein the collection comprising the sequence information of at least one of SEQ ID NO: 1-91.
 23. The collection of claim 22, wherein the collection is provided on a nucleic acid array.
 24. The collection of claim 23, wherein the array detects full-matches to any one of the polynucleotides in the collection.
 25. The collection of claim 23, wherein the array detects mismatches to any one of the polynucleotides in the collection.
 26. The collection of claim 22, wherein the collection is provided in a computer-readable format.
 27. A method of treatment comprising administering to a mammalian subject in need thereof a therapeutic amount of a composition comprising a polypeptide of claim 10 or 20 and a pharmaceutically acceptable carrier.
 28. A method of treatment comprising administering to a mammalian subject in need thereof a therapeutic amount of a composition comprising an antibody that specifically binds to a polypeptide of claim 10 or 20 and a pharmaceutically acceptable carrier. 